1. Academic Validation
  2. Interleukin-22 exacerbates angiotensin II-induced hypertensive renal injury

Interleukin-22 exacerbates angiotensin II-induced hypertensive renal injury

  • Int Immunopharmacol. 2022 Aug;109:108840. doi: 10.1016/j.intimp.2022.108840.
Wei Wang 1 Yang Lu 2 Xueling Hu 1 Huihui Li 3 Xiaozhao Li 1 Chenggen Xiao 4 Ting Meng 1 Ling Peng 1 Lu Gan 5 Qiaoling Zhou 1 Ping Xiao 1 Rong Tang 6
Affiliations

Affiliations

  • 1 Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 2 Department of Nephrology, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • 3 Department of Nephrology, Chongqing City Hospital of Traditional Chinese Medicine, Chongqing, China.
  • 4 Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 5 Department of Nephrology, First People's Hospital of Yunnan, Kunming, Yunnan, China.
  • 6 Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: [email protected].
Abstract

Hypertensive renal injury (HRI) is a main cause of end-stage renal diseases, and CD4+ T cells and the secreted inflammatory cytokines contribute to the progress of HRI. However, the exact mechanisms remain unidentified in HRI, and there is still a shortage of effective treatments. Here, we aim to explore the role of interleukin-22 (IL-22) and its underlying mechanism in HRI. Serum IL-22 level and peripheral Th22 cells frequency in patients with HRI were detected by ELISA and flow cytometry respectively. Angiotension II (Ang II) was infused subcutaneously to C57BL/6 mice for 28 days. Hypertensive mice were treated with recombinant IL-22 (rIL-22), anti-IL-22 antibody, or JAK2/STAT3 pathway blocker AG-490 respectively. Blood pressure (BP), urinary albumin/creatinine ratio (UACR), serum creatinine (Scr) and renal histopathology were measured; renal Th22 cells proportion were evaluated; inflammatory factors were evaluated by ELISA; JAK2/STAT3 pathway and fibrosis related factors expression in kidney were detected by Western blot. Serum IL-22 and Th22 cells proportion in kidney of mice were elevated after Ang II infusion. Compared to Ang II-infused mice, treatment with rIL-22 resulted in further increased UACR, Scr, renal pathological damage, inflammation and renal fibrosis, accompanied by elevated BP and JAK2/STAT3 pathway activation. Conversely, anti-IL-22 antibody reduced inflammation, renal fibrosis and BP in Ang II treated mice. AG490 could compromised the above effects of rIL-22. Taken together, recombinant IL-22 may aggravate hypertensive renal damage mediated by Ang II in mice, which may be through promoting JAK2/STAT3 pathway activation. Anti-IL-22 antibody exerts the opposite effects. These data suggest the IL-22 signaling maybe a novel therapeutic target for the treatment of hypertensive renal injury.

Keywords

Hypertensive renal injury; Inflammation; Interleukin-22; JAK2/STAT3 pathway; Renal fibrosis; Th22 cell.

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