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Hepatol Res. 2015 Jan;45(1):113-22. doi: 10.1111/hepr.12324. Epub 2014 Jul 4.

Nogo-B: A potential indicator for hepatic cirrhosis and regulator in hepatic stellate cell activation.

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1
Division of Digestive Diseases, West China Hospital, Sichuan University, Chengdu, China.

Abstract

AIM:

To evaluate plasma Nogo-B levels in liver cirrhotic patients and declare a novel molecular basis by which Nogo-B modulates hepatic stellate cell (HSC) activation.

METHODS:

Plasma Nogo-B levels from liver cirrhotic patients were detected by enzyme-linked immunosorbent assay. Rat primary HSC were culture activated or stimulated with transforming growth factor (TGF)-β. Activated HSC were transfected for 48 h with Nogo-B shRNA to inhibit Nogo-B expression. Gene expressions of Nogo-B, α-smooth muscle actin (SMA), collagen type I, TGF-β, endoplasmic reticulum (ER) stress key molecules, including C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), activating transcription factor (ATF)4, ATF6, X-box binding protein 1 (Xbp-1) and calnexin, and the marker of autophagy beclin 1, were detected by quantitative reverse transcription polymerase chain reaction. The protein expressions of Nogo-B, α-SMA, collagen type I, CHOP, GRP78 and the marker of autophagy LC3B were evaluated by western blot.

RESULTS:

Liver cirrhotic patients showed a much higher level of plasma Nogo-B compared with the healthy controls. Nogo-B expression and ER stress could be induced during the process of cultured HSC activation. TGF-β treatment increased Nogo-B expression time- and dose-dependently. Knockdown of Nogo-B in HSC reduced the activation of HSC. After Nogo-B gene knockdown, there was a decline of expression of ER stress markers and autophagic markers. Agonist or antagonist of ER stress could regulate autophagy level.

CONCLUSION:

Circulating Nogo-B may be an effective indicator for liver cirrhosis. Nogo-B inhibition could diminish HSC activation, in which alleviating ER stress may be one of the mechanisms, suggesting a potential approach to interference Nogo-B in liver fibrosis.

KEYWORDS:

Nogo-B; endoplasmic reticulum stress; hepatic stellate cells; shRNA; transforming growth factor-β

PMID:
24606149
DOI:
10.1111/hepr.12324
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