HO‑1 knockdown upregulates the expression of VCAM‑1 to induce neutrophil recruitment during renal ischemia‑reperfusion injury.
HO‑1 knockdown upregulates the expression of VCAM‑1 to induce neutrophil recruitment during renal ischemia‑reperfusion injury.
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DOI：
10.3892/ijmm.2021.5018
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发表时间：
2021-10
影响因子：
5.4
通讯作者：
Bian W
中科院分区：
文献类型：
--
作者：
He Y;Li H;Yao J;Zhong H;Kuang Y;Li X;Bian W
血红素氧合酶-1（HO-1）在肾缺血再灌注损伤（IRI）后表达上调，并发挥重要的细胞保护作用，但其保护作用的分子机制仍知之甚少。在本研究中，为了进一步阐明HO-1在肾IRI中的细胞保护作用的分子机制，HO-1+/+和HO-1+/−小鼠经历肾缺血和随后的再灌注，随后分析血尿素氮（BUN）和血清肌酐（SCr）水平，组织学变化的严重程度，HO-1和血管细胞粘附分子-1（VCAM-1）蛋白表达、炎症因子mRNA表达及阻断VCAM-1的影响。本研究的结果表明，在IRI期间HO-1+/−小鼠中VCAM-1的表达水平上调增加了肾组织损伤的程度并激活了炎症反应。这些作用随后在输注抗VCAM-1抗体后逆转。此外，从HO-1+/−小鼠分离的小鼠肾小球血管内皮细胞中VCAM-1的上调表达增加了中性粒细胞的粘附和迁移，这种作用在与抗VCAM-1抗体孵育后也被逆转。这些结果表明，HO-1敲低可能上调VCAM-1在肾IRI过程中的表达，导致增加的中性粒细胞募集和炎症反应的激活，从而加重肾IRI。因此，本研究强调HO-1在肾IRI中的调节机制，并为肾移植后IRI的临床治疗提供了潜在的靶点。
Heme oxygenase-1 (HO-1) has been reported to be upregulated following renal ischemia-reperfusion injury (IRI) and plays a key cytoprotective role; however, the underlying molecular mechanisms of its protective effects remain poorly understood. In the present study, in order to further elucidate the molecular mechanisms underlying the cytoprotective role of HO-1 in renal IRI, HO-1+/+ and HO-1+/− mice were subjected to renal ischemia and subsequent reperfusion followed by the analysis of blood urea nitrogen (BUN) and serum creatinine (SCr) levels, the severity of histological changes, HO-1 and vascular cell adhesion molecule-1 (VCAM-1) protein expression, the mRNA expression of inflammatory factors and the effects of VCAM-1 blockade. The results of the present study demonstrated that the upregulated expression levels of VCAM-1 in HO-1+/− mice during IRI increased the extent of renal tissue damage and activated the inflammatory response. These effects were subsequently reversed following infusion with an anti-VCAM-1 antibody. In addition, the upregulated expression of VCAM-1 in mouse glomerulus vascular endothelial cells isolated from HO-1+/− mice increased the adhesion and migration of neutrophils, effects which were also reversed upon incubation with an anti-VCAM-1 antibody. These results indicated that HO-1 knockdown may upregulate the expression of VCAM-1 during renal IRI, resulting in increased neutrophil recruitment and the activation of the inflammatory response, thereby exacerbating renal IRI. The present study thus highlights the regulatory mechanisms of HO-1 in renal IRI and provides a potential target for the clinical treatment of IRI following renal transplantation.