HO‑1 knockdown upregulates the expression of VCAM‑1 to induce neutrophil recruitment during renal ischemia‑reperfusion injury

He,Yecheng; Li,Huadong; Yao,Juan; Zhong,Hua; Kuang,Yanbin; Li,Xin; Bian,Weihua

doi:10.3892/ijmm.2021.5018

HO‑1 knockdown upregulates the expression of VCAM‑1 to induce neutrophil recruitment during renal ischemia‑reperfusion injury

Authors:
- Yecheng He
- Huadong Li
- Juan Yao
- Hua Zhong
- Yanbin Kuang
- Xin Li
- Weihua Bian
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Affiliations: Department of Clinical Medicine, Suzhou Vocational Health College, Suzhou, Jiangsu 215009, P.R. China, Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Nursing, Suzhou Vocational Health College, Suzhou, Jiangsu 215009, P.R. China, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, P.R. China, Department of Respiratory Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200123, P.R. China, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, P.R. China, Department of Cell Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Published online on: August 3, 2021 https://doi.org/10.3892/ijmm.2021.5018
Article Number: 185
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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