Essential Role of Matrix Metalloproteinases in Interleukin-1-induced Myofibroblastic Activation of Hepatic Stellate Cell in Collagen

Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis

“…[26][27][28] Other studies have shown that activated HSCs express MMP-13 in vivo 19 and in culture. 29,30 Cytokines, such as IL-1 and TGF-␤, stimulate MMP-13 production in cultured-HSCs, 30,31 which was also found in our study. It is likely the expression and activity of MMPs are regulated by the ECM environment via the integrin and/or DDR2 pathway, [31][32][33][34] and therefore upregulation of MMP-13 is found only in the context of a specific matrix environment, which was recapitulated in the BDL model system.…”

“…29,30 Cytokines, such as IL-1 and TGF-␤, stimulate MMP-13 production in cultured-HSCs, 30,31 which was also found in our study. It is likely the expression and activity of MMPs are regulated by the ECM environment via the integrin and/or DDR2 pathway, [31][32][33][34] and therefore upregulation of MMP-13 is found only in the context of a specific matrix environment, which was recapitulated in the BDL model system. These results indicate the pattern of expression of MMPs in HSCs may vary with the etiology and progression of the liver disease.…”

Physiological potential of cytokines and liver damages

“…Therefore, it is possible that genetic polymorphism of IL-1B gene may influence the progression of hepatic fibrosis by affecting the hepatic expression of IL-1 during the process of liver injury. [91] TGF-β has been implicated in hepatic fibrogensis; as it stimulates the production of extracellular matrix proteins and their receptors, and inhibits the synthesis of matrix-regrading proteolytic enzymes in chronic HCV; moreover, its serum or liver level has a positively correlation with the fibrosis score in both untreated patients or those respond to IFN-α treatment. [92] IL-10 has a protective role in hepatic fibrogenesis, as it showed a decreased hepatic inflammation and increased serum levels of HCV-RNA matched with reduced liver fibrosis score either in chronic HCVinfected patients who received a short or after 12 months therapy with recombinant IL-10.…”

Topical p38 MAPK inhibition reduces bacterial growth in an in vivo burn wound model

“…There is data to suggest that in skin inflammatory diseases cytokineinduced activation of pro-MMP is an important regulatory mechanism. 43, 44 We only looked at the total expression of MMP-2 and not the activation process. Whether p38 MAPK is an important regulatory mechanism for MMP-2 activation in our model remains to be elucidated.…”