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Kevin P. Lally - One of the best experts on this subject based on the ideXlab platform.
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MMP1 gene expression enhances myoblast migration and engraftment following implanting into mdx scid mice
Cell Adhesion & Migration, 2015Co-Authors: Haiying Pan, Kinga Vojnits, Thomas T Liu, Fanwei Meng, Lei Yang, Yigang Wang, Johnny Huard, Charles S. Cox, Kevin P. LallyAbstract:Myoblast transplantation (MT) is a method to introduce healthy genes into abnormal skeletal muscle. It has been considered as a therapeutic modality in the last few decades for diseases such as Duchenne Muscular Dystrophy (DMD). However, challenges including cell death and poor graft engraftment have limited its application. The current experiment utilizes MMP1 gene transfer to improve the efficacy of myoblast transplantation into the diseased dystrophic skeletal muscle of mdx mice. Our results indicated that MMP1 expression can promote myogenic differentiation and fusion capacities, increase migration of MMP1 expressing myoblasts in vitro, as well as improve engraftment of dystrophin positive myofibers in vivo. Taken together, our observation suggests that the addition of MMP1 can overcome limitations in MT and improve its clinical efficacy.
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MMP1 gene expression enhances myoblast migration and engraftment following implanting into mdx/SCID mice
Cell adhesion & migration, 2015Co-Authors: Haiying Pan, Kinga Vojnits, Thomas T Liu, Fanwei Meng, Lei Yang, Yigang Wang, Johnny Huard, Charles S. Cox, Kevin P. LallyAbstract:Myoblast transplantation (MT) is a method to introduce healthy genes into abnormal skeletal muscle. It has been considered as a therapeutic modality in the last few decades for diseases such as Duchenne Muscular Dystrophy (DMD). However, challenges including cell death and poor graft engraftment have limited its application. The current experiment utilizes MMP1 gene transfer to improve the efficacy of myoblast transplantation into the diseased dystrophic skeletal muscle of mdx mice. Our results indicated that MMP1 expression can promote myogenic differentiation and fusion capacities, increase migration of MMP1 expressing myoblasts in vitro, as well as improve engraftment of dystrophin positive myofibers in vivo. Taken together, our observation suggests that the addition of MMP1 can overcome limitations in MT and improve its clinical efficacy.
Maria Trojanowska - One of the best experts on this subject based on the ideXlab platform.
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Akt inhibition up-regulates MMP1 through a CCN2-dependent pathway in human dermal fibroblasts.
Experimental dermatology, 2010Co-Authors: Andreea M. Bujor, Sashidar Nakerakanti, Erin Morris, Faye N. Hant, Maria TrojanowskaAbstract:Akt is a key signalling molecule that was found to be down-regulated in chronic wounds. Akt blockade has dual antifibrotic effects in human dermal fibroblasts, by up-regulating matrix metalloproteinase 1 (MMP1) and down-regulating collagen gene expression (J Invest Dermatol 2008: 128: 1906). The aim of this study was to gain additional insights into the mechanism of MMP1 up-regulation following Akt blockade. As previous studies showed that CCN2 can be a positive regulator of MMP1, we examined the effects of Akt inhibition on CCN2 expression. Akt blockade using a specific pharmacological inhibitor and Akt siRNA resulted in a significant up-regulation of CCN2, which correlated with the increase in MMP1. The MMP1 up-regulation following Akt blockade was partially suppressed by CCN2 siRNA, suggesting that CCN2 is contributing to this effect. Additional experiments showed that CCN2 induces phosphorylation of ERK1/2, Ets1 and c-Jun. Consistent with the stimulatory role of ERK1/2/Ets1 in the expression of MMP1, the ERK1/2 inhibitor UO126 prevented the phosphorylation of ERK1/2 and Ets1 and completely abrogated the induction of MMP1 after CCN2 overexpression, while having no effect on c-Jun activation. Taken together these results establish CCN2 as a key regulator of MMP1 induction via activation of the ERK1/2/Ets1 pathway. Down-regulation of Akt signalling leads to inappropriate activation of the CCN2/MMP1 pathway that may contribute to the pathogenesis of chronic wounds. Coordinate expression of CCN2, Akt and MMP1 could be important for normal wound healing to occur. Thus, targeting these specific proteins may represent a promising approach to the therapy of dysregulated wound healing.
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dihydrosphingosine 1 phosphate stimulates MMP1 gene expression via activation of erk1 2 ets1 pathway in human fibroblasts
The FASEB Journal, 2006Co-Authors: Masayoshi Yamanaka, Huiping Pei, Alicja Bielawska, Jacek Bielawski, Yusuf A Hannun, Lina M Obeid, Maria TrojanowskaAbstract:SPECIFIC AIMSStudies have shown that sphingosine kinase 1 (SphK1) controls expression of TIMP1 (tissue inhibitor of metalloproteinase 1) gene in human fibroblast, suggesting that SphK1 may regulate cellular pathways involved in extracellular matrix (ECM) remodeling. To further investigate the involvement of SphK1 in this process, we focused on regulation of MMP1 (matrix metalloproteinase 1), a principal enzyme responsible for degradation of interstitial collagens.PRINCIPAL FINDINGS1. SphK1 is required for the TNFα stimulation of MMP1 in dermal fibroblasts through activation of the ERK1/2-Ets1 and NF-κB pathwaysTo determine the effect of SphK1 overexpression on MMP1 production, human dermal fibroblasts were transduced with adenoviral vector carrying SphK1 gene (SphK1Ad). SphK1 overexpression resulted in up-regulation of MMP1 protein and mRNA, as well as promoter activity in a dose-dependent and time-dependent manner, with a potency comparable to an MMP1 inducer, TNFα. To investigate the nature of the signa...
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Dihydrosphingosine 1-phosphate stimulates MMP1 gene expression via activation of ERK1/2-Ets1 pathway in human fibroblasts
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2005Co-Authors: Masayoshi Yamanaka, Huiping Pei, Alicja Bielawska, Jacek Bielawski, Yusuf A Hannun, Lina M Obeid, Maria TrojanowskaAbstract:SPECIFIC AIMSStudies have shown that sphingosine kinase 1 (SphK1) controls expression of TIMP1 (tissue inhibitor of metalloproteinase 1) gene in human fibroblast, suggesting that SphK1 may regulate cellular pathways involved in extracellular matrix (ECM) remodeling. To further investigate the involvement of SphK1 in this process, we focused on regulation of MMP1 (matrix metalloproteinase 1), a principal enzyme responsible for degradation of interstitial collagens.PRINCIPAL FINDINGS1. SphK1 is required for the TNFα stimulation of MMP1 in dermal fibroblasts through activation of the ERK1/2-Ets1 and NF-κB pathwaysTo determine the effect of SphK1 overexpression on MMP1 production, human dermal fibroblasts were transduced with adenoviral vector carrying SphK1 gene (SphK1Ad). SphK1 overexpression resulted in up-regulation of MMP1 protein and mRNA, as well as promoter activity in a dose-dependent and time-dependent manner, with a potency comparable to an MMP1 inducer, TNFα. To investigate the nature of the signa...
Haiying Pan - One of the best experts on this subject based on the ideXlab platform.
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MMP1 gene expression enhances myoblast migration and engraftment following implanting into mdx scid mice
Cell Adhesion & Migration, 2015Co-Authors: Haiying Pan, Kinga Vojnits, Thomas T Liu, Fanwei Meng, Lei Yang, Yigang Wang, Johnny Huard, Charles S. Cox, Kevin P. LallyAbstract:Myoblast transplantation (MT) is a method to introduce healthy genes into abnormal skeletal muscle. It has been considered as a therapeutic modality in the last few decades for diseases such as Duchenne Muscular Dystrophy (DMD). However, challenges including cell death and poor graft engraftment have limited its application. The current experiment utilizes MMP1 gene transfer to improve the efficacy of myoblast transplantation into the diseased dystrophic skeletal muscle of mdx mice. Our results indicated that MMP1 expression can promote myogenic differentiation and fusion capacities, increase migration of MMP1 expressing myoblasts in vitro, as well as improve engraftment of dystrophin positive myofibers in vivo. Taken together, our observation suggests that the addition of MMP1 can overcome limitations in MT and improve its clinical efficacy.
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MMP1 gene expression enhances myoblast migration and engraftment following implanting into mdx/SCID mice
Cell adhesion & migration, 2015Co-Authors: Haiying Pan, Kinga Vojnits, Thomas T Liu, Fanwei Meng, Lei Yang, Yigang Wang, Johnny Huard, Charles S. Cox, Kevin P. LallyAbstract:Myoblast transplantation (MT) is a method to introduce healthy genes into abnormal skeletal muscle. It has been considered as a therapeutic modality in the last few decades for diseases such as Duchenne Muscular Dystrophy (DMD). However, challenges including cell death and poor graft engraftment have limited its application. The current experiment utilizes MMP1 gene transfer to improve the efficacy of myoblast transplantation into the diseased dystrophic skeletal muscle of mdx mice. Our results indicated that MMP1 expression can promote myogenic differentiation and fusion capacities, increase migration of MMP1 expressing myoblasts in vitro, as well as improve engraftment of dystrophin positive myofibers in vivo. Taken together, our observation suggests that the addition of MMP1 can overcome limitations in MT and improve its clinical efficacy.
Andrea Staack - One of the best experts on this subject based on the ideXlab platform.
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In situ gene expression and localization of metalloproteinases MMP1, MMP2, MMP3, MMP9, and their inhibitors TIMP1 and TIMP2 in human renal cell carcinoma
Oncology reports, 2006Co-Authors: V. Bhuvarahamurthy, Glen Kristiansen, Manfred Johannsen, Stefan A. Loening, Dietmar Schnorr, Klaus Jung, Andrea StaackAbstract:Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a major role in the maintenance of extracellular matrix homeostasis. Alterations of MMP and TIMP expressions have been found in several malignant tumour entities. In this study the expression pattern of MMP1, MMP2, MMP3, MMP9, and their inhibitors TIMP1, and TIMP2 were investigated at mRNA and protein levels in human renal cell carcinoma (RCC). Formalin fixed paraffin embedded tumour samples of 10 patients and adjacent non-malignant controls were analysed by radioactive labelled riboprobe in situ hybridisation (isH) and immunohistochemistry. The slides were evaluated semiquantitatively. MMP1-antigen was strongly expressed in tumour epithelium with moderate stroma expression in one case. The gelatinases MMP2 and MMP9 showed moderate to strong signals in tumour epithelial cells at the mRNA and protein level, while the expression in tumour stroma was moderate. MMP3-mRNA and -antigen were expressed moderately to strong in tumour epithelium and focally in stroma cells. mRNA or TIMP1- and TIMP2-mRNA and -antigen were also predominantly expressed in tumour epithelium; only few samples showed positive expression in stroma cells. mRNA expression could be generally correlated to the protein expression in our study group, except for MMP1 (mRNA expression was only expressed in two cases). We found a pronounced expression for the gelatinases MMP2 and MMP9 and for MMP3 in RCC at the mRNA and protein level. The expression of TIMP1 and TIMP2 appears also to be relevant in RCC. Due to the small sample size further investigations need to be done to prove a statistical significant correlation between the MMP/TIMP expression and clinicopathological parameters.
Hongliang Zheng - One of the best experts on this subject based on the ideXlab platform.
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meta analysis of mmp2 mmp3 and mmp9 promoter polymorphisms and head and neck cancer risk
PLOS ONE, 2013Co-Authors: Caiyun Zhang, Minhui Zhu, Qingzhou Zhang, Zhenghua Xie, Gang Niu, Xicheng Song, Lei Jin, Hongliang ZhengAbstract:Background The 1306 C>T, 1171 5A>6A, and 1562C>T polymorphisms of matrix metalloproteinase (MMP) 2, MMP3, and MMP9 genes, respectively, have been found to be functional and may contribute to head and neck carcinogenesis. However, the results of case-control studies examining associations between MMP polymorphisms and head and neck cancer (HNC) risk remain inconclusive. Therefore, we performed a meta-analysis to further evaluate the role of these polymorphisms in HNC development.
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Association between MMP1 -1607 1G>2G Polymorphism and Head and Neck Cancer Risk: A Meta-Analysis
PloS one, 2013Co-Authors: Caiyun Zhang, Minhui Zhu, Xicheng Song, Lei Jin, Song Shi, Juntian Lang, Hongliang ZhengAbstract:Background MMP1 is an important member of the MMP endopeptidase family that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC, but their results have been inconsistent. Here, we conducted a meta-analysis to further explore the role of the MMP1 -1607 1G>2G polymorphism in HNC development.