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Jonathan L Eliason - One of the best experts on this subject based on the ideXlab platform.
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cigarette smoke induced mmp2 and MMP9 secretion from aortic vascular smooth cells is mediated via the jak stat pathway
Human Pathology, 2015Co-Authors: Abhijit Ghosh, Angela Pechota, Dawn M Coleman, Gilbert R Upchurch, Jonathan L EliasonAbstract:Summary It is hypothesized that cigarette smoke may increase MMP2 and MMP9 secretion through Jak/Stat pathway in the aorta, thereby facilitating abdominal aortic aneurysm (AAA) formation/progression in smokers. We observed through zymograms that treatment of male rat aortic vascular smooth muscle cells (RASMC) with an aqueous extract of cigarette smoke (CSE) for 24 hours resulted in a significant increase in pro-MMP9 ( P = .005) and a modest increase in pro-MMP2 ( P = .055) production. Western blot with protein extracts from CSE-treated RASMC showed up-regulation of pStat3, pJak2, and T-Jak2 and unchanged levels of T-Stat3. Transfection of RASMC with small interfering RNAs for Jak2, Stat3, or both Jak2 and Stat3 significantly reduced pro-MMP9 ( P P
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cigarette smoke induced mmp2 and MMP9 secretion from aortic vascular smooth cells is mediated via the jak stat pathway
Human Pathology, 2015Co-Authors: Abhijit Ghosh, Angela Pechota, Dawn M Coleman, Gilbert R Upchurch, Jonathan L EliasonAbstract:It is hypothesized that cigarette smoke may increase MMP2 and MMP9 secretion through Jak/Stat pathway in the aorta, thereby facilitating abdominal aortic aneurysm (AAA) formation/progression in smokers. We observed through zymograms that treatment of male rat aortic vascular smooth muscle cells (RASMC) with an aqueous extract of cigarette smoke (CSE) for 24 hours resulted in a significant increase in pro-MMP9 (P = .005) and a modest increase in pro-MMP2 (P = .055) production. Western blot with protein extracts from CSE-treated RASMC showed up-regulation of pStat3, pJak2, and T-Jak2 and unchanged levels of T-Stat3. Transfection of RASMC with small interfering RNAs for Jak2, Stat3, or both Jak2 and Stat3 significantly reduced pro-MMP9 (P < .005) and pro-MMP2 (P < .05) in medium of CSE-treated RASMC compared with control small interfering RNA-transfected cells. Immunoprecipitation with total Jak2 antibody showed increased pStat3 and T-Stat3 in the cytoplasm and nucleus of CSE-treated RASMC. Immunofluorescence revealed increased presence of pJak2, T-Jak2, pStat3, and T-Stat3 in the cytoplasm and nucleus of the CSE-treated cells. Treatment of control human tissues with CSE resulted in pro-MMP9 secretion and up-regulation of the Jak/Stat proteins. In addition, AAA tissues showed more pJak2 and pStat3 than control human tissues. Therefore, inhibiting the Jak/Stat pathway could be a potential therapeutic approach in the treatment of AAA.
Kid Törnquist - One of the best experts on this subject based on the ideXlab platform.
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sphingosine 1 phosphate attenuates mmp2 and MMP9 in human anaplastic thyroid cancer c643 cells importance of s1p2
PLOS ONE, 2018Co-Authors: Kid Törnquist, Muhammad Yasir Asghar, Kati Kemppainen, Taru LassilaAbstract:In anaplastic thyroid cancer C643 cells, sphingosine 1-phosphate (S1P) attenuates migration by activating the S1P2 receptor and the Rho-ROCK pathway. In the present study, we show that stimulating C643 cells with S1P decreases the expression, secretion and activity of matrix metalloproteinase-2 (MMP2), and to a lesser extent MMP9. Using receptor-specific antagonists, and S1P2 siRNA, we showed that the inhibition of expression of MMP2 is mediated through S1P2. Furthermore, S1P inhibited calpain activity, and inhibiting calpain pharmacologically, inhibited the effect of S1P on MMP2 expression and activity, and on MMP9 activity. S1P treatment increased Rho activity, and by incubating cells with the Rho inhibitor C3 transferase or the ROCK inhibitor Y27632, the S1P-induced inhibition of invasion and MMP2 expression and activity was abolished. We conclude that S1P attenuates the invasion of C643 cells by activating S1P2 and the Rho-ROCK pathway, by decreasing calpain activity, and by decreasing the expression, secretion and activity of MMP2 and, to a lesser extent, MMP9. Our results thus unveil a novel function for the S1P2 receptor in attenuating thyroid cancer cell invasion.
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mmp2 and MMP9 participate in s1p induced invasion of follicular ml 1 thyroid cancer cells
Molecular and Cellular Endocrinology, 2015Co-Authors: Veronica Kalhori, Kid TörnquistAbstract:The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion.
Clemens Unger - One of the best experts on this subject based on the ideXlab platform.
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Development and in vitro efficacy of novel MMP2 and MMP9 specific doxorubicin albumin conjugates
Bioorganic & Medicinal Chemistry Letters, 2001Co-Authors: Felix Kratz, Joachim Drevs, Gerlinde Bing, Cornelia Stockmar, Karin Scheuermann, Peter Lazar, Clemens UngerAbstract:Abstract Two doxorubicin albumin conjugates ( A-DP1 and A-DP2 ), which differ in their substrate specificity for the matrix metalloproteinases MMP2 and MMP9, were prepared by binding maleimide doxorubicin peptide derivatives to the cysteine-34 position of human serum albumin. The incorporated octapeptide, Gly-Pro-Gln-Arg–Ile-Ala-Gly-Gln, in A-DP2 is not cleaved by activated MMP2 and MMP9 in contrast to Gly-Pro-Leu-Gly–Ile-Ala-Gly-Gln incorporated in A-DP1 that is cleaved efficiently by activated MMP2 and MMP9 liberating a doxorubicin tetrapeptide. A-DP1 showed antiproliferative activity in a murine renal cell carcinoma line in the low micromolar range (IC 50 value≈0.2 μM).
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development and in vitro efficacy of novel mmp2 and MMP9 specific doxorubicin albumin conjugates
Bioorganic & Medicinal Chemistry Letters, 2001Co-Authors: Felix Kratz, Joachim Drevs, Gerlinde Bing, Cornelia Stockmar, Karin Scheuermann, Peter Lazar, Clemens UngerAbstract:Two doxorubicin albumin conjugates (A-DP1 and A-DP2), which differ in their substrate specificity for the matrix metalloproteinases MMP2 and MMP9, were prepared by binding maleimide doxorubicin peptide derivatives to the cysteine-34 position of human serum albumin. The incorporated octapeptide, Gly-Pro-Gln-Arg-Ile-Ala-Gly-Gln, in A-DP2 is not cleaved by activated MMP2 and MMP9 in contrast to Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln incorporated in A-DP1 that is cleaved efficiently by activated MMP2 and MMP9 liberating a doxorubicin tetrapeptide. A-DP1 showed antiproliferative activity in a murine renal cell carcinoma line in the low micromolar range (IC(50) value approximately 0.2 microM).
Abhijit Ghosh - One of the best experts on this subject based on the ideXlab platform.
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cigarette smoke induced mmp2 and MMP9 secretion from aortic vascular smooth cells is mediated via the jak stat pathway
Human Pathology, 2015Co-Authors: Abhijit Ghosh, Angela Pechota, Dawn M Coleman, Gilbert R Upchurch, Jonathan L EliasonAbstract:Summary It is hypothesized that cigarette smoke may increase MMP2 and MMP9 secretion through Jak/Stat pathway in the aorta, thereby facilitating abdominal aortic aneurysm (AAA) formation/progression in smokers. We observed through zymograms that treatment of male rat aortic vascular smooth muscle cells (RASMC) with an aqueous extract of cigarette smoke (CSE) for 24 hours resulted in a significant increase in pro-MMP9 ( P = .005) and a modest increase in pro-MMP2 ( P = .055) production. Western blot with protein extracts from CSE-treated RASMC showed up-regulation of pStat3, pJak2, and T-Jak2 and unchanged levels of T-Stat3. Transfection of RASMC with small interfering RNAs for Jak2, Stat3, or both Jak2 and Stat3 significantly reduced pro-MMP9 ( P P
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cigarette smoke induced mmp2 and MMP9 secretion from aortic vascular smooth cells is mediated via the jak stat pathway
Human Pathology, 2015Co-Authors: Abhijit Ghosh, Angela Pechota, Dawn M Coleman, Gilbert R Upchurch, Jonathan L EliasonAbstract:It is hypothesized that cigarette smoke may increase MMP2 and MMP9 secretion through Jak/Stat pathway in the aorta, thereby facilitating abdominal aortic aneurysm (AAA) formation/progression in smokers. We observed through zymograms that treatment of male rat aortic vascular smooth muscle cells (RASMC) with an aqueous extract of cigarette smoke (CSE) for 24 hours resulted in a significant increase in pro-MMP9 (P = .005) and a modest increase in pro-MMP2 (P = .055) production. Western blot with protein extracts from CSE-treated RASMC showed up-regulation of pStat3, pJak2, and T-Jak2 and unchanged levels of T-Stat3. Transfection of RASMC with small interfering RNAs for Jak2, Stat3, or both Jak2 and Stat3 significantly reduced pro-MMP9 (P < .005) and pro-MMP2 (P < .05) in medium of CSE-treated RASMC compared with control small interfering RNA-transfected cells. Immunoprecipitation with total Jak2 antibody showed increased pStat3 and T-Stat3 in the cytoplasm and nucleus of CSE-treated RASMC. Immunofluorescence revealed increased presence of pJak2, T-Jak2, pStat3, and T-Stat3 in the cytoplasm and nucleus of the CSE-treated cells. Treatment of control human tissues with CSE resulted in pro-MMP9 secretion and up-regulation of the Jak/Stat proteins. In addition, AAA tissues showed more pJak2 and pStat3 than control human tissues. Therefore, inhibiting the Jak/Stat pathway could be a potential therapeutic approach in the treatment of AAA.
Xuming Zhu - One of the best experts on this subject based on the ideXlab platform.
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association between matrix metalloproteinase polymorphisms and prostate cancer risk a meta analysis and systematic review
Cancer management and research, 2018Co-Authors: Hongxing Zhou, Xuming ZhuAbstract:Background Data from published articles on the relationship between MMP polymorphisms and prostate cancer risk are conflicted and inconclusive, so a meta-analysis and systematic review were performed to assess the relationship. Methods Relevant research articles were identified from databases using a search strategy. Studies with the same MMP polymorphisms that could be quantitatively synthesized were included in the meta-analysis. Five comparison models (homozygote, heterozygote, dominant, recessive, and additive) were applied, and a subgroup analysis by case-group sample type was performed. Studies with different polymorphisms that could not be quantitatively synthesized were included in the systematic review. Results Eleven articles encompassing 22 studies involving 12 MMP polymorphisms were included in this paper. Among the studies included, 13 studies involving MMP1 rs1799750, MMP2 rs243865, and MMP7 rs11568818 were quantitatively synthesized for meta-analysis, and the other nine studies involving nine polymorphisms (MMP2 rs2285053, MMP2 rs1477017, MMP2 rs17301608, MMP2 rs11639960, MMP3 11715A/6A, MMP3 1161A/G, MMP3 5356A/G, MMP9 rs17576, and MMP13 rs2252070) were included in the systematic review. Meta-analysis showed no associations between MMP1 rs1799750, MMP2 rs243865, or MMP7 rs11568818 and prostate cancer risk overall. Subgroup analysis by case-group sample type confirmed that no associations existed. The systematic review suggested that MMP3 11715A/6A and MMP9 rs17576 were associated with prostate cancer risk. Conclusion MMP polymorphisms are not associated with prostate cancer risk, except for MMP3 11715A/6A and MMP9 rs17576. However, it is necessary to conduct larger-scale, high-quality studies in future.
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association between matrix metalloproteinases polymorphisms and ovarian cancer risk a meta analysis and systematic review
PLOS ONE, 2017Co-Authors: Xuming Zhu, Weifeng SunAbstract:Background Published data on the relationship between matrix metalloproteinases (MMPs) polymorphisms and ovarian cancer risk have implicated inconclusive results. To evaluate the role of MMPs polymorphisms in ovarian cancer risk, a meta-analysis and systematic review were performed. Methods MMPs polymorphisms which could be quantitatively synthesized were involved in meta-analysis. Five comparison models (homozygote model, heterozygote model, dominant model, recessive model, additive model) were carried out, a subgroup analysis was performed to clarify heterogeneity source. The remaining polymorphisms which could not be quantitatively synthesized were involved in systematic review. Results 10 articles with 20 studies were included in this paper. Among those studies, 8 studies involving MMP1 rs1799750 and MMP3 rs34093618 could be meta-analyzed and 12 studies involving 12 polymorphisms could not. Meta-analysis showed that no associations were found between MMP1 rs1799750 (homozygote model: OR = 0.93, 95%CI = 0.70–1.23, POR = 0.60; heterozygote model: OR = 1.09, 95%CI = 0.78–1.54, POR = 0.61; dominant model: OR = 1.02, 95%CI = 0.83–1.25, POR = 0.84; recessive model: OR = 0.95, 95%CI = 0.75–1.21, POR = 0.67; additive model: OR = 1.00, 95%CI = 0.85–1.17, POR = 0.99), MMP3 rs34093618 (homozygote model: OR = 1.25, 95%CI = 0.70–2.24, POR = 0.46; heterozygote model: OR = 1.08, 95%CI = 0.51–2.31, POR = 0.84; dominant model: OR = 0.97, 95%CI = 0.68–1.38, POR = 0.85; recessive model: OR = 1.12, 95%CI = 0.69–1.80, POR = 0.65; additive model: OR = 1.01, 95%CI = 0.79–1.31, POR = 0.91) and ovarian cancer. Furthermore, similar results were detected in subgroup analysis. The systematic review on 12 polymorphisms suggested that MMP2 C-735T, MMP7 A-181G, MMP8 rs11225395, MMP9 rs6094237, MMP12 rs2276109, MMP20 rs2292730, MMP20 rs12278250, MMP20 rs9787933 might have a potential effect on ovarian cancer risk. Conclusions In summary, polymorphisms of MMPs might not be associated with ovarian cancer risk. However, it is necessary to conduct more larger-scale, multicenter, and high-quality studies in the future.