Telmisartan Plus Propranolol Improves Liver Fibrosis and Bile Duct Proliferation in the PSC-Like Abcb4−/− Mouse Model

Abstract

Telmisartan plus propranolol reduces liver fibrosis and bile duct proliferation in the PSC-like Abcb4 (-/-) mouse model, even when started at late stages of fibrosis, and may thus represent a novel therapeutic option for cholestatic liver diseases such as PSC.

Treatment of glaucoma by prostaglandin agonists and beta‐blockers in combination directly reduces pro‐fibrotic gene expression in trabecular meshwork

“…The role of beta‐adrenergic signalling in driving TGFβ expression and fibrosis‐associated changes in cardiac tissues has been reported 48,49 . Beta‐blockers have been shown to reduce pro‐fibrotic mediators and fibrotic changes in liver and cardiac tissues in animal models 50‐52 . TM tissues have been shown to express beta‐adrenergic receptors 53,54 and was observed to be present in hTM cells and TM tissues from the current study cohort (Figure S6).…”

“…48,49 Beta-blockers have been shown to reduce pro-fibrotic mediators and fibrotic changes in liver and cardiac tissues in animal models. [50][51][52] TM tissues have been shown to express beta-adrenergic receptors 53,54 and was observed to be present in hTM cells and TM tissues from the current study cohort (Figure S6). This suggests the plausibility of beta-blockers regulating fibrosis-associated mechanisms in the TM.…”

Telmisartan inhibits the non-canonical TGF-β/JAK2/STAT3 signaling pathway and prevents carbon tetrachloride-induced liver fibrosis in rats

“…HSCs activation due to liver injury goes along with TGF-β1 release from activated Kupffer cells that participate in hepatic fibrosis 38 . Many reports documented that blockage of RAS mitigates liver fibrosis 39 . These findings are in line with our results in which CCl4-intoxication result in marked elevation in hepatic TGF-β1level.…”

Biliary epithelium: A neuroendocrine compartment in cholestatic liver disease

“…α-1 adrenergic receptor stimulation increases collagen deposition from HSCs, presumably in a calcium signaling-dependent manner 28 . The total number of HSCs and activated HSCs, as well as liver fibrosis progression, was reduced by chemical sympathectomy and treatment with adrenergic blocking drugs 3233 . Furthermore, cholangiocytes express all adrenergic receptor subtypes and activation of α-1 receptors by catecholamines stimulate the growth of small cholangiocytes by activating the IP 3 /Ca 2+ /calmodulin pathway 34 .…”