Bevacizumab Attenuates Hepatic Fibrosis in Rats by Inhibiting Activation of Hepatic Stellate Cells

Abstract

Angiogenesis is a fundamental part of the response to tissue injury, which is involved in the development of hepatic fibrosis. Vascular endothelial growth factor plays an important role in angiogenesis. The expression of VEGF is increased during hepatic fibrogenesis and correlates with the micro-vessel density. In this study, we investigated the effects of bevacizumab, an anti-angiogenetic drug, on the formation of hepatic fibrosis. We found that bevacizumab could attenuate the development of hepatic fibrosis and contribute to the protection of liver function. Bevacizumab was also found to downregulate the expression α-SMA and TGF-β1, which have been reported to be profibrogenic genes in vivo. We also observed that the expression of VEGF increased significantly during the development of hepatic fibrosis and CCl4 was found to induce hepatocytes to secrete VEGF, which led to the activation and proliferation of HSCs. Bevacizumab was also found to block the effects of the hepatocytes on the activation and proliferation of HSCs. Our results suggest that bevacizumab might alleviate liver fibrosis by blocking the effect of VEGF on HSCs. Bevacizumab might be suitable as a potential agent for hepatic fibrosis therapy.

Astragaloside Alleviates Hepatic Fibrosis Function via PAR2 Signaling Pathway in Diabetic Rats

“…A recent study suggests that the activation of the hepatic stellate cell causes accumulation of extracellular matrix and formation of scar, leading to deterioration in the hepatic functions [3]. The hepatic stellate cells are also called Ito cells, which store fat, produce excessive amounts of abnormal matrix including collagen, other glycoproteins and glycans, and matricellular proteins [4].…”

Stellate Cells and Portal Hypertension

“…Further, angiopoietin-1, the ligand for the tyrosine kinase with immunoglobulin G-like and endothelial growth factor-like domains 2 (Tie2) receptor, which has angiogenic properties, is produced by stellate cells [112]. Additionally, blocking Tie2 signaling inhibited angiogenesis and experimental hepatic fibrosis [112] and bevacizumab, an anti-angiogenic agent, attenuated angiogenesis and hepatic fibrosis [113]. These data suggest that stellate cells may stimulate angiogenesis.…”

Differential Roles of Angiogenesis in the Induction of Fibrogenesis and the Resolution of Fibrosis in Liver

“…39) In rat liver fibrosis models, treatment with bevacizumab alleviates liver fibrosis by neutralizing VEGF produced by hepatocytes and blocking its effects for the activation of HSCs. 40) Recent anti-angiogenic approaches include use of the multiple receptor tyrosine kinase inhibitor Sorafenib to target the Raf/extracellular signal-regulated kinase (ERK) and PDGFR-β signaling cascade, as well as the VEGFR signaling pathway. Sorafenib treatment attenuates liver fibrosis and is associated with significant decreases in intrahepatic fibrogenesis and collagen deposition.…”