Department of Anesthesiology, The First Hospital of Jilin University, Changchun, Jilin, China.
FASEB J. 2024 Jul 31;38(14):e23823. doi: 10.1096/fj.202400843R.
Hepatic ischemia-reperfusion injury (HIRI) represents a major risk factor in liver transplantation and resection surgeries. Kupffer cells (KCs) produce proinflammatory cytokines and lead to hepatic neutrophil infiltration in the liver, which is one of the leading causes of HIRI. Mid1 is involved in immune infiltration, but the role of Mid1 remains poorly understood. Herin, our study aimed to investigate the effect of Mid1 on HIRI progression. Male C57BL/6 mice aged 6 weeks were used for the HIRI model established. The function of Mid1 on liver injury and hepatic inflammation was evaluated. In vitro, KCs were used to investigate the function and mechanism of Mid1 in modulating KC inflammation upon lipopolysaccharide (LPS) stimulation. We found that Mid1 expression was up-regulated upon HIRI. Mid1 inhibition alleviated liver damage, as evidenced by neutrophil infiltration, intrahepatic inflammation, and hepatocyte apoptosis. In vitro experiments further revealed that Mid1 knockdown reduced the secretion of proinflammatory cytokines and chemokines in KCs. Moreover, silenced-Mid1 suppressed proinflammatory responses by the inhibition of NF-κB, JNK, and p38 signaling pathways. Taken together, Mid1 contributes to HIRI via regulating the proinflammatory response of KCs and inducing neutrophil infiltration. Targeting Mid1 may be a promising strategy to protect against HIRI.
肝缺血再灌注损伤 (HIRI) 是肝移植和肝切除术的主要危险因素。库普弗细胞 (KCs) 产生促炎细胞因子，并导致肝脏中性粒细胞浸润，这是 HIRI 的主要原因之一。Mid1 参与免疫浸润，但 Mid1 的作用仍知之甚少。在本研究中，我们旨在研究 Mid1 对 HIRI 进展的影响。使用 6 周龄雄性 C57BL/6 小鼠建立 HIRI 模型。评估 Mid1 对肝损伤和肝炎症的功能。在体外，使用 KCs 研究 Mid1 在 LPS 刺激下调节 KC 炎症的功能和机制。我们发现 HIRI 时 Mid1 表达上调。Mid1 抑制减轻了肝损伤，表现为中性粒细胞浸润、肝内炎症和肝细胞凋亡。体外实验进一步表明，沉默 Mid1 通过抑制 NF-κB、JNK 和 p38 信号通路减少 KCs 中促炎细胞因子和趋化因子的分泌。总之，Mid1 通过调节 KCs 的促炎反应和诱导中性粒细胞浸润导致 HIRI。靶向 Mid1 可能是一种有前途的策略，可用于预防 HIRI。
