In vitro effects of INT747 and losartan on the AT‐II‐ and LPS‐induced proliferation, mRNA expressions of TGF‐β1, TLR4, and Myd88, and NF‐κB and Smad signaling pathways in Ac‐HSCs. (A) AT‐II and LPS treatment resulted in a significant increase in Ac‐HSC proliferation. The administration of losartan alone or combined INT747 and losartan significantly inhibited the effects of AT‐II and LPS. Treatment with INT747 did not significantly attenuate Ac‐HSC proliferation. AT‐II and LPS treatment significantly increased mRNA expressions of (B) TGF‐β1, (C) TLR4, and (D) Myd88 and phosphorylation of (E) NF‐κB, (F) Smad2, and (G) Smad3. AT‐II‐ and LPS‐induced mRNA expression of TGF‐β1, TLR4, and Myd88 and phosphorylation of NF‐κB and Smad3 were individually suppressed by INT747 or losartan. Combined therapy exerted more potent suppression than monotherapy with either agent. The administration of losartan alone or combined therapy significantly reduced AT‐II‐ and LPS‐induced Smad2 phosphorylation, whereas INT747 alone had no significant effect on Smad2 phosphorylation. Values represent mean ± SD (bars, n = 8). Asterisks indicate significant differences between indicated experimental groups (*P < 0.05, **P < 0.01). Abbreviation: N.S, not significant.