Induction of tropomyosin during hepatic stellate cell activation and the progression of liver fibrosis

Abstract

The activation of hepatic stellate cells (HSCs) is a cue to initiate liver fibrosis. Activated stellate cells acquire contractile activity similar to pericytes and myofibroblasts in other organs by inducing the contractile machinery of cytoskeletons such as smooth muscle alpha-actin (alpha-SMA), a well-known marker of activated stellate cells, and actin-binding proteins. We further show herein the expression of tropomyosin in rat HSCs in the course of their activation during primary culture and liver tissue damaged by thioacetamide intoxication. In immunoblot analysis, tropomyosin became detectable in an early stage of the primary culture of rat stellate cells in a manner similar to the expression of alpha-SMA and platelet-derived growth factor receptor-beta. Tropomyosin was found to be colocalized with alpha-SMA on fluorescent immunocytochemistry. At the liver tissue level, an increased expression of tropomyosin was observed by immunoblot analysis and immunohistochemistry along the septum of fibrosis, where alpha-SMA was enriched. These results strongly suggest that tropomyosin is a new marker of activated stellate cells and may serve as a useful diagnostic marker of liver fibrosis.

miR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by HIF-α activation

“…Fibroblasts and epithelial cells express high-mo- lecular-weight (HMW) tropomyosin isoforms TM2, TM3, and TM6 encoded by the TPM1 gene and TM1 encoded by TPM2. While we have not directly studied the role of TPM1 in fibrosis, TPM1 has been reported as stress fibers that are responsible for ECM deposition (13) and epithelial mesenchymal transformation (EMT) (35,58) or a biomarker of liver fibrosis (34,37) and was reported to play an important role in the pathogenesis of endomyocardial fibrosis (6). In the current study, we used the well-characterized TM311 antibody against tropomyosin, which recognizes up to three bands that presumably correspond to tropomyosin isoforms TM2, TM3, and TM6.…”

Interleukin‐9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice

“…The myofibroblasts can migrate to the necrotic tissue and the area of inflammation. Meanwhile, they have a powerful ability to produce α ‐smooth‐muscle actin ( α ‐SMA) and collagens, the main components of extracellular matrix …”

“…Meanwhile, they have a powerful ability to produce a-smooth-muscle actin (a-SMA) and collagens, the main components of extracellular matrix. 5 CD4 + helper T (Th) cells play pivotal roles in both host humoral immunity and cellular immunity against parasitic infection and immunopathology in schistosomiasis by secreting a variety of cytokines and providing help to other cells. After infection, antigen secreted by schistosome eggs induces a continuous immune response of CD4 + T cells.…”

Anti-fibrotic effects of Acremoniumterricola milleretal mycelium on immunological hepatic fibrosis in rats

“…HSCs have a key function in the pathogenesis of fibrosis (26,27). Upon the activation of HSCs, levels of fibrillar collagen, particularly types I and II, become markedly increased.…”