Periostin cross‑reacts with the renin‑angiotensin system during liver fibrosis development.

Abstract

Periostin is a 90‑kDa extracellular matrix protein, which is secreted primarily from fibroblasts and is expressed in the lungs, kidneys and heart valves. Angiotensin II (AT‑II) serves pivotal roles in the pathogenesis of several diseases with accompanying fibrosis, including chronic liver diseases. AT‑II induces periostin expression by regulating transforming growth factor‑β1 (TGF‑β1)/Smad signaling during cardiac fibrosis. The aim of the present study was to investigate the interaction between AT‑II and periostin during liver fibrosis development. Fischer 344 rats were fed a choline‑deficient L‑amino‑acid (CDAA)‑defined diet for 12 weeks to simulate the development of steatohepatitis with liver fibrosis. Losartan, an AT‑II type I receptor blocker, was administered to inhibit the effect of AT‑II. The therapeutic effect of losartan on hepatic fibrosis development and on periostin expression was then evaluated. Several in vitro experiments were performed to examine the mechanisms underlying the interaction between AT‑II and periostin in activated hepatic stellate cells (Ac‑HSCs). Treatment with losartan suppressed the development of liver fibrosis induced by the CDAA diet, and reduced hepatic periostin expression. In addition, losartan treatment suppressed hepatic Ac‑HSC expansion and hepatic TGF‑β1 expression. In vitro analysis using LX2 HSC cells indicated that AT‑II can augment TGF‑β1 and collagen type I α1 mRNA expression via periostin expression, suggesting that the interaction between AT‑II and periostin may serve a role in liver fibrosis development. In conclusion, blockade of AT‑II‑induced periostin may suppress the progression of liver fibrosis development.

• Authors: Kosuke Takeda, Ryuichi Noguchi, Mitsuteru Kitade, Tadashi Namisaki, Kei Moriya, Hideto Kawaratani, Yasushi Okura, Kosuke Kaji, Yosuke Aihara, Akitoshi Douhara, Norihisa Nishimura, Yasuhiko Sawada, Kenichiro Seki, Hitoshi Yoshiji
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 16 Issue 5 Pg. 5752-5758 (Nov 2017) ISSN: 1791-3004 [Electronic] Greece
• PMID: 28849131 (Publication Type: Journal Article)

Chemical References

• Cell Adhesion Molecules
• Collagen Type I
• Collagen Type I, alpha 1 Chain
• Postn protein, rat
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• Angiotensin II
• Losartan

Topics

• Angiotensin II (genetics)
• Animals
• Cell Adhesion Molecules (genetics)
• Collagen Type I (genetics)
• Collagen Type I, alpha 1 Chain
• Gene Expression Regulation (genetics)
• Hepatic Stellate Cells (drug effects, metabolism)
• Humans
• Liver (metabolism, pathology)
• Liver Cirrhosis (genetics, pathology)
• Losartan (administration & dosage)
• Rats
• Renin-Angiotensin System (genetics)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta1 (genetics)