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炎症细胞浸润增加加重肝缺血再灌注损伤与 TGF-β/Smad3 信号通路有关。

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

机构信息

Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.

Key Laboratory of Endoscopic Technology Research, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China.

出版信息

Mol Med Rep. 2021 Aug;24(2). doi: 10.3892/mmr.2021.12219. Epub 2021 Jun 16.

Abstract

Ischemia‑reperfusion (IR) injury is a major challenge 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 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 aminotransferase (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 littermates received the sham operation. Histopathological changes in liver tissues and serum levels of ALT were then compared between the groups. Furthermore, hepatic apoptosis and inflammatory 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. Aggravated hepatic injury, increased apoptosis and enhanced inflammatory cell infiltration induced by hepatic IR injury were observed in the Smad3 mice compared with in Smad3 mice. Collectively, the current findings suggested that activation of the TGF‑β/Smad3 signaling pathway was present alongside the hepatic injury induced by IR. However, the TGF‑β/Smad3 signaling pathway may have an effect on protecting against liver tissue damage caused by IR injury .

摘要

缺血再灌注(IR)损伤是影响肝移植结局的主要挑战。转化生长因子-β(TGF-β)及其下游基因 SMAD 家族成员 3(Smad3)已被认为与慢性肝损伤的发病机制有关,如肝纤维化。因此,本研究旨在探讨 TGF-β/Smad3 信号通路在 IR 诱导的肝损伤中的作用。共将 20 只 129S2/SvPasCrl 野生型(WT)小鼠随机分为两组;10 只小鼠接受 IR 损伤手术,10 只小鼠进行假手术。通过检测肝组织的组织病理学变化和血清丙氨酸氨基转移酶(ALT)水平来证实 IR 手术后的肝损伤。通过 Western blot 检测 TGF-β1、Smad3 和磷酸化 Smad3(p-Smad3)的表达水平。此外,5 只 Smad3 129S2/SvPasCrl 小鼠(Smad3 小鼠)和 10 只 Smad3 同窝小鼠接受 IR 手术,另 5 只 Smad3 小鼠和 10 只 Smad3 同窝小鼠接受假手术。然后比较各组肝组织的组织病理学变化和血清 ALT 水平。此外,还评估了 Smad3 小鼠和 Smad3 小鼠肝组织中 IR 后肝凋亡和炎症细胞浸润情况。结果表明,WT 小鼠 IR 损伤后肝组织中 TGF-β1、Smad3 和 p-Smad3 的表达水平升高。与 Smad3 小鼠相比,Smad3 小鼠的肝 IR 损伤引起的肝损伤加重、凋亡增加和炎症细胞浸润增强。综上所述,目前的研究结果表明,IR 诱导的肝损伤存在 TGF-β/Smad3 信号通路的激活。然而,TGF-β/Smad3 信号通路可能对保护 IR 损伤引起的肝组织损伤有一定作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f525/8223105/47f404f2688c/mmr-24-02-12219-g00.jpg

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