The Experts below are selected from a list of 243183 Experts worldwide ranked by ideXlab platform
Kamal Chowdhury - One of the best experts on this subject based on the ideXlab platform.
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MiR-132 controls pancreatic beta cell proliferation and survival through Pten/Akt/ Foxo3 signaling
Molecular metabolism, 2020Co-Authors: Hassan Mziaut, Kamal Chowdhury, Georg Henniger, Katharina Ganss, Sebastian Hempel, Steffen Wolk, Johanna Mcchord, Philippe Ravassard, Klaus-peter Knoch, Christian KrautzAbstract:OBJECTIVE: MicroRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains challenging. In this study, we aimed to identify miRNAs and their downstream targets involved in the regeneration of islet beta cells following partial pancreatectomy in mice. METHODS: RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in beta cell regeneration. Altered expression of the selected miRNAs, including MiR-132, was verified by RT-PCR. Potential targets of MiR-132 were selected through bioinformatic data mining. Predicted MiR-132 targets were validated for their changed RNA, protein expression levels, and signaling upon MiR-132 knockdown and/or overexpression in mouse MIN6 and human EndoC-βH1 insulinoma cells. The ability of MiR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized MiR-132-/- and control mice. RESULTS: Partial pancreatectomy significantly increased the number of BrdU+/insulin+ islet cells. Microarray profiling revealed that 14 miRNAs, including MiR-132 and -141, were significantly upregulated in the LCM islets of the partially pancreatectomized mice compared to the LCM islets of the control mice. In the same comparison, miR-760 was the only downregulated miRNA. The changed expression of these miRNAs in the islets of the partially pancreatectomized mice was confirmed by RT-PCR only in the case of MiR-132 and -141. Based on previous knowledge of its function, we focused our attention on MiR-132. Downregulation of MiR-132 reduced the proliferation of MIN6 cells while enhancing the levels of pro-apoptotic cleaved caspase-9. The opposite was observed in MiR-132 overexpressing MIN6 cells. Microarray profiling, RT-PCR, and immunoblotting of the latter cells demonstrated their downregulated expression of Pten with concomitant increased levels of pro-proliferative factors phospho-Akt and phospho-Creb and inactivation of pro-apoptotic Foxo3a via its phosphorylation. Downregulation of Pten was further confirmed in the LCM islets of pancreatectomized mice compared to the sham-operated mice. Moreover, overexpression of MiR-132 correlated with increased proliferation of EndoC-βH1 cells. The regeneration of beta cells following partial pancreatectomy was lower in the MiR-132/212-/- mice than the control littermates. CONCLUSIONS: This study provides compelling evidence about the critical role of MiR-132 for the regeneration of mouse islet beta cells through the downregulation of its target Pten. Hence, the MiR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass.
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MiR-132 controls pancreatic beta cell proliferation and survival through Pten/Akt/Foxo3 signaling
Molecular metabolism, 2019Co-Authors: Hassan Mziaut, Kamal Chowdhury, Georg Henniger, Katharina Ganss, Sebastian Hempel, Steffen Wolk, Johanna Mcchord, Philippe Ravassard, Klaus-peter Knoch, Christian KrautzAbstract:Abstract Objective MicroRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains challenging. In this study, we aimed to identify miRNAs and their downstream targets involved in the regeneration of islet beta cells following partial pancreatectomy in mice. Methods RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in beta cell regeneration. Altered expression of the selected miRNAs, including MiR-132, was verified by RT-PCR. Potential targets of MiR-132 were selected through bioinformatic data mining. Predicted MiR-132 targets were validated for their changed RNA, protein expression levels, and signaling upon MiR-132 knockdown and/or overexpression in mouse MIN6 and human EndoC-βH1 insulinoma cells. The ability of MiR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized MiR-132−/− and control mice. Results Partial pancreatectomy significantly increased the number of BrdU+/insulin+ islet cells. Microarray profiling revealed that 14 miRNAs, including MiR-132 and -141, were significantly upregulated in the LCM islets of the partially pancreatectomized mice compared to the LCM islets of the control mice. In the same comparison, miR-760 was the only downregulated miRNA. The changed expression of these miRNAs in the islets of the partially pancreatectomized mice was confirmed by RT-PCR only in the case of MiR-132 and -141. Based on previous knowledge of its function, we focused our attention on MiR-132. Downregulation of MiR-132 reduced the proliferation of MIN6 cells while enhancing the levels of pro-apoptotic cleaved caspase-9. The opposite was observed in MiR-132 overexpressing MIN6 cells. Microarray profiling, RT-PCR, and immunoblotting of the latter cells demonstrated their downregulated expression of Pten with concomitant increased levels of pro-proliferative factors phospho-Akt and phospho-Creb and inactivation of pro-apoptotic Foxo3a via its phosphorylation. Downregulation of Pten was further confirmed in the LCM islets of pancreatectomized mice compared to the sham-operated mice. Moreover, overexpression of MiR-132 correlated with increased proliferation of EndoC-βH1 cells. The regeneration of beta cells following partial pancreatectomy was lower in the MiR-132/212−/− mice than the control littermates. Conclusions This study provides compelling evidence about the critical role of MiR-132 for the regeneration of mouse islet beta cells through the downregulation of its target Pten. Hence, the MiR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass.
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the microrna 212 132 cluster regulates b cell development by targeting sox4
Journal of Experimental Medicine, 2015Co-Authors: Erdem Erikci, Arnav Mehta, Mati Mann, Jimmy L Zhao, Georgi K Marinov, Devdoot Majumdar, Yvette Garciaflores, Kamal ChowdhuryAbstract:MicroRNAs have emerged as key regulators of B cell fate decisions and immune function. Deregulation of several microRNAs in B cells leads to the development of autoimmune disease and cancer in mice. We demonstrate that the microRNA-212/132 cluster (miR-212/132) is induced in B cells in response to B cell receptor signaling. Enforced expression of MiR-132 results in a block in early B cell development at the prepro–B cell to pro–B cell transition and induces apoptosis in primary bone marrow B cells. Importantly, loss of miR-212/132 results in accelerated B cell recovery after antibody-mediated B cell depletion. We find that Sox4 is a target of MiR-132 in B cells. Co-expression of SOX4 with MiR-132 rescues the defect in B cell development from overexpression of MiR-132 alone, thus suggesting that MiR-132 may regulate B lymphopoiesis through Sox4. In addition, we show that the expression of MiR-132 can inhibit cancer development in cells that are prone to B cell cancers, such as B cells expressing the c-Myc oncogene. We have thus uncovered MiR-132 as a novel contributor to B cell development.
Hassan Mziaut - One of the best experts on this subject based on the ideXlab platform.
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MiR-132 controls pancreatic beta cell proliferation and survival through Pten/Akt/ Foxo3 signaling
Molecular metabolism, 2020Co-Authors: Hassan Mziaut, Kamal Chowdhury, Georg Henniger, Katharina Ganss, Sebastian Hempel, Steffen Wolk, Johanna Mcchord, Philippe Ravassard, Klaus-peter Knoch, Christian KrautzAbstract:OBJECTIVE: MicroRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains challenging. In this study, we aimed to identify miRNAs and their downstream targets involved in the regeneration of islet beta cells following partial pancreatectomy in mice. METHODS: RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in beta cell regeneration. Altered expression of the selected miRNAs, including MiR-132, was verified by RT-PCR. Potential targets of MiR-132 were selected through bioinformatic data mining. Predicted MiR-132 targets were validated for their changed RNA, protein expression levels, and signaling upon MiR-132 knockdown and/or overexpression in mouse MIN6 and human EndoC-βH1 insulinoma cells. The ability of MiR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized MiR-132-/- and control mice. RESULTS: Partial pancreatectomy significantly increased the number of BrdU+/insulin+ islet cells. Microarray profiling revealed that 14 miRNAs, including MiR-132 and -141, were significantly upregulated in the LCM islets of the partially pancreatectomized mice compared to the LCM islets of the control mice. In the same comparison, miR-760 was the only downregulated miRNA. The changed expression of these miRNAs in the islets of the partially pancreatectomized mice was confirmed by RT-PCR only in the case of MiR-132 and -141. Based on previous knowledge of its function, we focused our attention on MiR-132. Downregulation of MiR-132 reduced the proliferation of MIN6 cells while enhancing the levels of pro-apoptotic cleaved caspase-9. The opposite was observed in MiR-132 overexpressing MIN6 cells. Microarray profiling, RT-PCR, and immunoblotting of the latter cells demonstrated their downregulated expression of Pten with concomitant increased levels of pro-proliferative factors phospho-Akt and phospho-Creb and inactivation of pro-apoptotic Foxo3a via its phosphorylation. Downregulation of Pten was further confirmed in the LCM islets of pancreatectomized mice compared to the sham-operated mice. Moreover, overexpression of MiR-132 correlated with increased proliferation of EndoC-βH1 cells. The regeneration of beta cells following partial pancreatectomy was lower in the MiR-132/212-/- mice than the control littermates. CONCLUSIONS: This study provides compelling evidence about the critical role of MiR-132 for the regeneration of mouse islet beta cells through the downregulation of its target Pten. Hence, the MiR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass.
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MiR-132 controls pancreatic beta cell proliferation and survival through Pten/Akt/Foxo3 signaling
Molecular metabolism, 2019Co-Authors: Hassan Mziaut, Kamal Chowdhury, Georg Henniger, Katharina Ganss, Sebastian Hempel, Steffen Wolk, Johanna Mcchord, Philippe Ravassard, Klaus-peter Knoch, Christian KrautzAbstract:Abstract Objective MicroRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains challenging. In this study, we aimed to identify miRNAs and their downstream targets involved in the regeneration of islet beta cells following partial pancreatectomy in mice. Methods RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in beta cell regeneration. Altered expression of the selected miRNAs, including MiR-132, was verified by RT-PCR. Potential targets of MiR-132 were selected through bioinformatic data mining. Predicted MiR-132 targets were validated for their changed RNA, protein expression levels, and signaling upon MiR-132 knockdown and/or overexpression in mouse MIN6 and human EndoC-βH1 insulinoma cells. The ability of MiR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized MiR-132−/− and control mice. Results Partial pancreatectomy significantly increased the number of BrdU+/insulin+ islet cells. Microarray profiling revealed that 14 miRNAs, including MiR-132 and -141, were significantly upregulated in the LCM islets of the partially pancreatectomized mice compared to the LCM islets of the control mice. In the same comparison, miR-760 was the only downregulated miRNA. The changed expression of these miRNAs in the islets of the partially pancreatectomized mice was confirmed by RT-PCR only in the case of MiR-132 and -141. Based on previous knowledge of its function, we focused our attention on MiR-132. Downregulation of MiR-132 reduced the proliferation of MIN6 cells while enhancing the levels of pro-apoptotic cleaved caspase-9. The opposite was observed in MiR-132 overexpressing MIN6 cells. Microarray profiling, RT-PCR, and immunoblotting of the latter cells demonstrated their downregulated expression of Pten with concomitant increased levels of pro-proliferative factors phospho-Akt and phospho-Creb and inactivation of pro-apoptotic Foxo3a via its phosphorylation. Downregulation of Pten was further confirmed in the LCM islets of pancreatectomized mice compared to the sham-operated mice. Moreover, overexpression of MiR-132 correlated with increased proliferation of EndoC-βH1 cells. The regeneration of beta cells following partial pancreatectomy was lower in the MiR-132/212−/− mice than the control littermates. Conclusions This study provides compelling evidence about the critical role of MiR-132 for the regeneration of mouse islet beta cells through the downregulation of its target Pten. Hence, the MiR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass.
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332-LB: MiR-132 Controls Pancreatic Beta-Cell Proliferation and Survival through the Pten/Akt/Foxo3 Signaling
Diabetes, 2019Co-Authors: Stephan Kersting, Hassan MziautAbstract:Aim and Hypothesis: microRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. We aimed to identify miRNAs and their downstream targets involved in regeneration of islet beta cells following partial pancreatectomy (pP) in mice. Methods: RNA from laser capture microdissected islets of pP and sham-operated mice were profiled with microarrays to identify miRNAs implicated in control of beta cell regeneration. Altered expression of selected miRNAs, including MiR-132, was verified by RT-PCR. Potential targets of MiR-132 were selected through bioinformatic data mining. Predicted MiR-132 targets were validated for their changed RNA and protein expression levels and signaling upon MiR-132 knockdown and overexpression in mouse MIN6 cells and human EndoC-βH1 insulinoma cells. The ability of MiR-132 to foster beta cell proliferation in vivo was further assessed in pP MiR-132 -/- and control mice. Results: pP significantly increased the number of BrdU+/insulin+ positive islet cells. Microarray profiling revealed 14 miRNAs, including MiR-132, to be significantly upregulated in LCM islets of partially pancreatectomized mice and confirmed by RT-PCR. Downregulation of MiR-132 in MIN6 cells reduced proliferation while enhancing the levels of pro-apoptotic cleaved caspase-9. Microarray profiling, RT-PCR and immunoblotting revealed downregulated expression of Pten, with concomitant increased levels of pro-proliferative factors as well as inactivation of pro-apoptotic Foxo3. Overexpression of MiR-132 in human insulinoma cells EndoC-βH1 validated the findings. In vivo regeneration of beta cells was reduced in pP MiR-132 -/- mice compared to control mice. Conclusions: Our study provides compelling evidence for MiR-132 being critical for regeneration of mouse islet beta cells in vivo through downregulation of its target Pten. Hence, the MiR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell regeneration. Disclosure S. Kersting: None. H. Mziaut: None. Funding German Center for Diabetes Research (to S.K.)
Christian Krautz - One of the best experts on this subject based on the ideXlab platform.
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MiR-132 controls pancreatic beta cell proliferation and survival through Pten/Akt/ Foxo3 signaling
Molecular metabolism, 2020Co-Authors: Hassan Mziaut, Kamal Chowdhury, Georg Henniger, Katharina Ganss, Sebastian Hempel, Steffen Wolk, Johanna Mcchord, Philippe Ravassard, Klaus-peter Knoch, Christian KrautzAbstract:OBJECTIVE: MicroRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains challenging. In this study, we aimed to identify miRNAs and their downstream targets involved in the regeneration of islet beta cells following partial pancreatectomy in mice. METHODS: RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in beta cell regeneration. Altered expression of the selected miRNAs, including MiR-132, was verified by RT-PCR. Potential targets of MiR-132 were selected through bioinformatic data mining. Predicted MiR-132 targets were validated for their changed RNA, protein expression levels, and signaling upon MiR-132 knockdown and/or overexpression in mouse MIN6 and human EndoC-βH1 insulinoma cells. The ability of MiR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized MiR-132-/- and control mice. RESULTS: Partial pancreatectomy significantly increased the number of BrdU+/insulin+ islet cells. Microarray profiling revealed that 14 miRNAs, including MiR-132 and -141, were significantly upregulated in the LCM islets of the partially pancreatectomized mice compared to the LCM islets of the control mice. In the same comparison, miR-760 was the only downregulated miRNA. The changed expression of these miRNAs in the islets of the partially pancreatectomized mice was confirmed by RT-PCR only in the case of MiR-132 and -141. Based on previous knowledge of its function, we focused our attention on MiR-132. Downregulation of MiR-132 reduced the proliferation of MIN6 cells while enhancing the levels of pro-apoptotic cleaved caspase-9. The opposite was observed in MiR-132 overexpressing MIN6 cells. Microarray profiling, RT-PCR, and immunoblotting of the latter cells demonstrated their downregulated expression of Pten with concomitant increased levels of pro-proliferative factors phospho-Akt and phospho-Creb and inactivation of pro-apoptotic Foxo3a via its phosphorylation. Downregulation of Pten was further confirmed in the LCM islets of pancreatectomized mice compared to the sham-operated mice. Moreover, overexpression of MiR-132 correlated with increased proliferation of EndoC-βH1 cells. The regeneration of beta cells following partial pancreatectomy was lower in the MiR-132/212-/- mice than the control littermates. CONCLUSIONS: This study provides compelling evidence about the critical role of MiR-132 for the regeneration of mouse islet beta cells through the downregulation of its target Pten. Hence, the MiR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass.
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MiR-132 controls pancreatic beta cell proliferation and survival through Pten/Akt/Foxo3 signaling
Molecular metabolism, 2019Co-Authors: Hassan Mziaut, Kamal Chowdhury, Georg Henniger, Katharina Ganss, Sebastian Hempel, Steffen Wolk, Johanna Mcchord, Philippe Ravassard, Klaus-peter Knoch, Christian KrautzAbstract:Abstract Objective MicroRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains challenging. In this study, we aimed to identify miRNAs and their downstream targets involved in the regeneration of islet beta cells following partial pancreatectomy in mice. Methods RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in beta cell regeneration. Altered expression of the selected miRNAs, including MiR-132, was verified by RT-PCR. Potential targets of MiR-132 were selected through bioinformatic data mining. Predicted MiR-132 targets were validated for their changed RNA, protein expression levels, and signaling upon MiR-132 knockdown and/or overexpression in mouse MIN6 and human EndoC-βH1 insulinoma cells. The ability of MiR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized MiR-132−/− and control mice. Results Partial pancreatectomy significantly increased the number of BrdU+/insulin+ islet cells. Microarray profiling revealed that 14 miRNAs, including MiR-132 and -141, were significantly upregulated in the LCM islets of the partially pancreatectomized mice compared to the LCM islets of the control mice. In the same comparison, miR-760 was the only downregulated miRNA. The changed expression of these miRNAs in the islets of the partially pancreatectomized mice was confirmed by RT-PCR only in the case of MiR-132 and -141. Based on previous knowledge of its function, we focused our attention on MiR-132. Downregulation of MiR-132 reduced the proliferation of MIN6 cells while enhancing the levels of pro-apoptotic cleaved caspase-9. The opposite was observed in MiR-132 overexpressing MIN6 cells. Microarray profiling, RT-PCR, and immunoblotting of the latter cells demonstrated their downregulated expression of Pten with concomitant increased levels of pro-proliferative factors phospho-Akt and phospho-Creb and inactivation of pro-apoptotic Foxo3a via its phosphorylation. Downregulation of Pten was further confirmed in the LCM islets of pancreatectomized mice compared to the sham-operated mice. Moreover, overexpression of MiR-132 correlated with increased proliferation of EndoC-βH1 cells. The regeneration of beta cells following partial pancreatectomy was lower in the MiR-132/212−/− mice than the control littermates. Conclusions This study provides compelling evidence about the critical role of MiR-132 for the regeneration of mouse islet beta cells through the downregulation of its target Pten. Hence, the MiR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass.
Yangmei Chen - One of the best experts on this subject based on the ideXlab platform.
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MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process.
Neural Plasticity, 2016Co-Authors: Jinxian Yuan, Shu Ou, Ruohan Li, Limin Ma, Hao Huang, Xin Zhou, Tao Xu, Yangmei ChenAbstract:Increasing evidence suggests that epilepsy is the result of synaptic reorganization and pathological excitatory loop formation in the central nervous system; however, the mechanisms that regulate this process are not well understood. We proposed that microRNA-132 (MiR-132) and p250GAP might play important roles in this process by activating the downstream Rho GTPase family. We tested this hypothesis using a magnesium-free medium-induced epileptic model of cultured hippocampal neurons. We investigated whether MiR-132 regulates GTPase activity through p250GAP and found that Cdc42 was significantly activated in our experimental model. Silencing MiR-132 inhibited the electrical excitability level of cultured epileptic neurons, whereas silencing p250GAP had an opposite effect. In addition, we verified the effect of MiR-132 in vivo and found that silencing MiR-132 inhibited the aberrant formation of dendritic spines and chronic spontaneous seizure in a lithium-pilocarpine-induced epileptic mouse model. Finally, we confirmed that silencing MiR-132 has a neuroprotective effect on cultured epileptic neurons; however, this effect did not occur through the p250GAP pathway. Generally, silencing MiR-132 may suppress spontaneous seizure activity through the MiR-132/p250GAP/Cdc42 pathway by regulating the morphology and electrophysiology of dendritic spines; therefore, MiR-132 may serve as a potential target for the development of antiepileptic drugs.
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microrna 132 interact with p250gap cdc42 pathway in the hippocampal neuronal culture model of acquired epilepsy and associated with epileptogenesis process
Neural Plasticity, 2016Co-Authors: Jinxian Yuan, Shu Ou, Ruohan Li, Hao Huang, Xin Zhou, Tao Xu, Yangmei ChenAbstract:Increasing evidence suggests that epilepsy is the result of synaptic reorganization and pathological excitatory loop formation in the central nervous system; however, the mechanisms that regulate this process are not well understood. We proposed that microRNA-132 (MiR-132) and p250GAP might play important roles in this process by activating the downstream Rho GTPase family. We tested this hypothesis using a magnesium-free medium-induced epileptic model of cultured hippocampal neurons. We investigated whether MiR-132 regulates GTPase activity through p250GAP and found that Cdc42 was significantly activated in our experimental model. Silencing MiR-132 inhibited the electrical excitability level of cultured epileptic neurons, whereas silencing p250GAP had an opposite effect. In addition, we verified the effect of MiR-132 in vivo and found that silencing MiR-132 inhibited the aberrant formation of dendritic spines and chronic spontaneous seizure in a lithium-pilocarpine-induced epileptic mouse model. Finally, we confirmed that silencing MiR-132 has a neuroprotective effect on cultured epileptic neurons; however, this effect did not occur through the p250GAP pathway. Generally, silencing MiR-132 may suppress spontaneous seizure activity through the MiR-132/p250GAP/Cdc42 pathway by regulating the morphology and electrophysiology of dendritic spines; therefore, MiR-132 may serve as a potential target for the development of antiepileptic drugs.
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MicroRNA-132 silencing decreases the spontaneous recurrent seizures.
International journal of clinical and experimental medicine, 2014Co-Authors: Yunyi Huang, Jing Guo, Qian Wang, Yangmei ChenAbstract:Objective: This study aimed to investigate the role of microRNA-132 in the epileptogenesis. Methods: AntagoMiR-132 (Ant-132) was used to silence the expression of MiR-132 and non-targeting scrambled sequence (Scr) as a control. Rats were randomly divided into ant-132 group and Scr group in which rats were pretreated with An-132 and Scr, respectively, and then induced temporal lobe epilepsy (TLE) by Li-Pilo. Behavioral observation was done, and results showed the changes in spontaneous recurrent seizures in the chronic phase between two groups. Bax and Bcl-2 were detected aiming to evaluate the neuronal apoptosis. NPY staining was done to investigate the mossy fiber sprouting (MFS). Golgi staining was used to assess the changes in the dendritic morphology. Results: Our study showed that ant-132 induced MiR-132 silencing in rats could increase the on-set epilepsy threshold and suppress the numbers of spontaneous recurrent seizures. The number of apoptotic neurons and MFS reduced after MiR-132 silencing. In addition, the dendrites of neurons were highly suppressed in the CA3 region of the hippocampus. Conclusions: MiR-132 silencing suppresses the spontaneous seizures. The better outcome may result from the neuroprotective effect and the inhibition of MFs-CA3 pathway following MiR-132 silencing. Thus, MiR-132 may serve as a potential target for the development of anti-epileptic drugs.
Karl Swärd - One of the best experts on this subject based on the ideXlab platform.
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Detrusor induction of MiR-132/212 following bladder outlet obstruction: association with MeCP2 repression and cell viability.
PloS one, 2015Co-Authors: Mardjaneh Karbalaei Sadegh, Olga Göransson, Mari Ekman, Katarzyna K. Krawczyk, Daniel Svensson, Diana Dahan, Bengt-olof Nilsson, Sebastian Albinsson, Bengt Uvelius, Karl SwärdAbstract:The microRNAs (miRNAs) MiR-132 and miR-212 have been found to regulate synaptic plasticity and cholinergic signaling and recent work has demonstrated roles outside of the CNS, including in smooth muscle. Here, we examined if MiR-132 and miR-212 are induced in the urinary bladder following outlet obstruction and whether this correlates with effects on gene expression and cell growth. Three to seven-fold induction of MiR-132/212 was found at 10 days of obstruction and this was selective for the detrusor layer. We cross-referenced putative binding sites in the MiR-132/212 promoter with transcription factors that were predicted to be active in the obstruction model. This suggested involvement of Creb and Ahr in MiR-132/212 induction. Creb phosphorylation (S-133) was not increased, but the number of Ahr positive nuclei increased. Moreover, we found that serum stimulation and protein kinase C activation induced MiR-132/212 in human detrusor cells. To identify MiR-132/212 targets, we correlated the mRNA levels of validated targets with the miRNA levels. Significant correlations between MiR-132/212 and MeCP2, Ep300, Pnkd and Jarid1a were observed, and the protein levels of MeCP2, Pnkd and Ache were reduced after obstruction. Reduction of Ache however closely matched a 90% reduction of synapse density arguing that its repression was unrelated to MiR-132/212 induction. Importantly, transfection of antimirs and mimics in cultured detrusor cells increased and decreased, respectively, the number of cells and led to changes in MeCP2 expression. In all, these findings show that obstruction of the urethra increases MiR-132 and miR-212 in the detrusor and suggests that this influences gene expression and limits cell growth.
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detrusor induction of mir 132 212 following bladder outlet obstruction association with mecp2 repression and cell viability
PLOS ONE, 2015Co-Authors: Mardjaneh Karbalaei Sadegh, Olga Göransson, Mari Ekman, Katarzyna K. Krawczyk, Daniel Svensson, Diana Dahan, Bengt-olof Nilsson, Sebastian Albinsson, Bengt Uvelius, Karl SwärdAbstract:The microRNAs (miRNAs) MiR-132 and miR-212 have been found to regulate synaptic plasticity and cholinergic signaling and recent work has demonstrated roles outside of the CNS, including in smooth muscle. Here, we examined if MiR-132 and miR-212 are induced in the urinary bladder following outlet obstruction and whether this correlates with effects on gene expression and cell growth. Three to seven-fold induction of MiR-132/212 was found at 10 days of obstruction and this was selective for the detrusor layer. We cross-referenced putative binding sites in the MiR-132/212 promoter with transcription factors that were predicted to be active in the obstruction model. This suggested involvement of Creb and Ahr in MiR-132/212 induction. Creb phosphorylation (S-133) was not increased, but the number of Ahr positive nuclei increased. Moreover, we found that serum stimulation and protein kinase C activation induced MiR-132/212 in human detrusor cells. To identify MiR-132/212 targets, we correlated the mRNA levels of validated targets with the miRNA levels. Significant correlations between MiR-132/212 and MeCP2, Ep300, Pnkd and Jarid1a were observed, and the protein levels of MeCP2, Pnkd and Ache were reduced after obstruction. Reduction of Ache however closely matched a 90% reduction of synapse density arguing that its repression was unrelated to MiR-132/212 induction. Importantly, transfection of antimirs and mimics in cultured detrusor cells increased and decreased, respectively, the number of cells and led to changes in MeCP2 expression. In all, these findings show that obstruction of the urethra increases MiR-132 and miR-212 in the detrusor and suggests that this influences gene expression and limits cell growth.