Wnt-induced secreted protein 1/CCN4 in liver fibrosis both in vitro and in vivo.

BACKGROUND: Wnt-induced secreted protein-1 (WISP-1/CCN4) is a member of the CCN family growth factors, and its role in liver fibrosis is largely unknown. METHODS: For in vitro, hepatic stellate cells (HSCs) were isolated from Sprague-Dawley rats. Expression of WISP-1 during progressive activation of cultured rat HSCs was analyzed by qRT-PCR. The effects of TNF-a and TGF-beta1 on WISP-1 expression were analyzed in stellate cell lines HSC-T6 and LX-2. The effect of exogenous WISP-1 protein on LX-2 proliferation was examined. For in vivo, expressions of WISP-1 in fibrotic liver of a carbon tetrachloride (CCl4)-induced fibrosis rat model were analyzed by qRT-PCR and immunohistochemistry. RESULTS: In vitro, WISP-1 was increasingly expressed during progressive activation of cultured rat HSCs. WISP-1 was significantly induced in HSC-T6 cells by TNF-a and in LX-2 cells by TGF-beta1. Recombinant WISP-1 protein promoted LX-2 proliferation in a dose-dependent manner. In vivo, both mRNA and protein expression levels of WISP-1 were increased significantly in experimental hepatic fibrosis model. CONCLUSIONS: Our results showed the upregulation of WISP-1 in both in vitro and in vivo liver fibrosis models, and WISP-1 stimulated the proliferation of HSCs in vitro. These results may be helpful to elucidate the exact role of WISP-1 in liver fibrogenesis.

The effect of carvedilol and propranolol on portal hypertension in patients with cirrhosis: a meta-analysis.

PURPOSE: Several randomized controlled clinical trials have been conducted to investigate the role of carvedilol and propranolol on the effect of portal pressure in patients with cirrhosis, leading to controversial results. Current meta-analysis was performed to compare the efficacy of the two drugs on portal pressure. PATIENTS AND METHODS: Two-hundred and ninety eligible patients were recruited. Published studies were selected based on PubMed, the Cochrane Library, Chinese Journal Full-text Database, and Wanfang Database. The outcome measurements included the mean difference (MD) in the percentage of hepatic vein pressure gradient reduction (%HVPG reduction), the risk ratio (RR) of nonresponders in hemodynamic assessment, and the percentage of mean arterial pressure reduction (%MAP reduction). Subgroup analysis was performed. RESULTS: Seven trials were identified (including five acute and three long-term drug administration randomized controlled trials). A summary of pooled MD between the %HVPG reduction is as follows: overall -8.62 (confidence interval [CI] -11.76, -5.48, P<0.00001), acute -10.05 (CI -14.24, -5.86, P<0.00001), and long term -6.80 (CI -11.53, -2.07, P=0.005), while summary of pooled RR of hemodynamic nonresponders with carvedilol was as follows: overall 0.64 (CI 0.51, 0.81, P=0.0002), acute 0.63 (CI 0.47, 0.85, P=0.002), and long term 0.67 (CI 0.47, 0.97, P=0.03). Both of the outcome measurements favored carvedilol. Significant heterogeneity (P<0.1, I (2)=92%) existed between the two treatment groups in %MAP reduction. No considerable difference could be observed in the %MAP reduction through the poor overlapping CI boundaries. CONCLUSION: Carvedilol has a greater portal hypertensive effect than propranolol. Further comparative trials of the two drugs are required to identify the effect of MAP reduction.