Aggravation of hepatic ischemia‑reperfusion injury with increased inflammatory cell infiltration is associated with the TGF‑β/Smad3 signaling pathway

Abstract

Ischemia‑reperfusion (IR) injury is a major chal‑ lenge influencing the outcomes of hepatic transplantation. Transforming growth factor‑β (TGF‑β) and its downstream gene, SMAD family member 3 (Smad3), have been implicated in the pathogenesis of chronic hepatic injuries, such as hepatic fibrosis. Thus, the present study aimed to investigate the role of the TGF‑β/Smad3 signaling pathway on hepatic injury induced by IR in vivo. In total, 20 129S2/SvPasCrl wild‑type (WT) mice were randomized into two groups; 10 mice underwent IR injury surgery and 10 mice were sham‑operated. Histopathological changes in liver tissues and serum levels of alanine aminotrans‑ ferase (ALT) were examined to confirm hepatic injury caused by IR surgery. The expression levels of TGF‑β1, Smad3 and phosphorylated‑Smad3 (p‑Smad3) were detected via western blotting. Furthermore, a total of five Smad3‑/‑ 129S2/SvPasCrl mice (Smad3‑/‑ mice) and 10 Smad3+/+ littermates received IR surgery, while another five Smad3‑/‑ mice and 10 Smad3+/+ litter‑ mates received the sham operation. Histopathological changes in liver tissues and serum levels of ALT were then compared between the groups. Furthermore, hepatic apoptosis and inflam‑ matory cell infiltration after IR were evaluated in the liver tissues of Smad3‑/‑ mice and Smad3+/+ mice. The results demonstrated that the expression levels of TGF‑β1, Smad3 and p‑Smad3 were elevated in hepatic tissue from WT mice after IR injury.