To further investigate the occurrence mechanism of diabetic hepatic fibrosis through observing the effects of insulin and glucose in different concentrations on hepatic stellate cell (HSC) proliferation, and mRNA expressions of transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rats, so as to provide a theoretical and experimental basis for the occurrence, prevention and treatment of diabetic hepatic fibrosis (HF).
This study verified differential expression of MMPs and TIMPs in different stages of BA, with emphasis on the role of TIMP-1, -2, and -3 as well as MMP-2, -7, and -9 transcripts in remodeling of liver tissue during the progress of BA-associated liver fibrosis.
Furthermore, we detected the key factors involved in liver fibrosis in the mice, revealing significantly increased hydroxyproline concentration; elevated expression of α-smooth muscle actin (α-SMA) and fibrosis-related genes such as Collagen-1, Collagen-3, Mmp2, Mmp13, Timp1, Timp3, and Activin, upregulated Smad3 phosphorylation, and increased serum TGF-β levels.
Salidroside inhibited the production of extracellular matrix (ECM) and regulated the balance between MMP2 and TIMP1 and, therefore, alleviated liver fibrosis in the two fibrosis models.
Transplantation of FGF21_ADSCs significantly improved liver fibrosis by decreasing serum hyaluronic acid and reducing the expression of fibrosis-related factors such as α-smooth muscle actin (α-SMA), collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) compared with the Empty_ADSCs by inhibition of p-JNK, NF-κB and p-Smad2/3 signalling.
The mechanism of anti-fibrotic effect of yangonin was that yangonin reduced collagen content by regulating the genes involved in hepatic fibrosis including COL1-α1 and TIMP-1.
During spontaneous recovery from liver fibrosis, there is a decrease of TIMP expression, an increase in collagenase activity, and increased apoptosis of HSC, highlighting a potential role for TIMP-1 in HSC survival.
Consistent with the results of in vitro study, intrahepatic IFN-γ/STAT1 levels increased in relation to the severity of liver fibrosis in BA patients, and the altered balance between MMP2 and TIMP1 expressions in livers may contribute to increased deposition of extracellular matrix and fibrosis.
A farnesoid x receptor-small heterodimer partner regulatory cascade modulates tissue metalloproteinase inhibitor-1 and matrix metalloprotease expression in hepatic stellate cells and promotes resolution of liver fibrosis.
In this retrospective, observational study, we analyzed 91 protocol liver biopsy specimens from 73 children after pediatric liver transplantation (PLT) and compared histological stage of liver fibrosis using LAF Score (LAFSc) and Ishak Score (IshakSc) to TIMP1-serum concentration and APRI using ROC analysis.
Panax ginseng extract and ginsenoside Rb1 attenuate plasma aminotransferase activities and liver inflammation to inhibit CCl4-induced liver fibrosis through down-regulation of hepatic prostaglandin E2 and TIMP-1.
Compared with CCl<sub>4</sub> injection alone, CCl<sub>4</sub> plus LPS injection exaggerated liver fibrosis in mice, as demonstrated by increased Col1a1 (collagen, type I, α 1), Acta2, Tgfb and Timp1 mRNA expression, ACTA2/α-SMA and COL1A1 protein expression, and Sirius Red staining area, which could be attenuated by injection of an autophagy inhibitor.
Bile duct injury induces an altered expression of TGF-beta, which has an important role in liver fibrosis because this cytokine induces the expression of target genes such as collagens, PAI-1, TIMPs, and others that lead to extracellular matrix deposition.
Areas under the receiver operating characteristic (AUROC) curve for advanced fibrosis were not significantly different between the direct markers of liver fibrosis (hyaluronate, PIIINP, TIMP-1, alpha2-macroglobulin) and the simple blood fibrosis tests NFS and FIB4.
These data indicate that hepatic lipocytes can regulate matrix degradation in the liver, and suggest that expression of TIMP-1 by activated lipocytes may contribute to the progression of liver fibrosis.