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Abstract: SA-PO311

The Role of the JAK2/STAT3 Pathway Activated by IL-22 in Angiotensin II-Induced Hypertensive Renal-Damage Mice

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Author

  • Tang, Rong, Xiangya Hospital, Central South University, Changsha, China
Background

CD4+T cells and the secreted inflammatory cytokines contribute to the progress of hypertensive renal damage. Previously, we found that blood Th22 cells and its effect factor IL-22 increased significantly in hypertensive renal damage patients, and were positively correlated with renal pathological damage. It is reported that IL-22 binds to receptor IL-22R and activates JAK2/STAT3 pathway. Th22 cells and its secreted cytokine IL-22 may play a promoting role in hypertensive renal damage, however the effects and mechanisms remain unclear.

Methods

Angiotension II (Ang II) was infused subcutaneously at a rate of 1.5 mg/kg/d to C57BL/6 mice for 28 days. Hypertensive mice were treated with recombinant IL-22 (rIL-22), anti-IL-22 neutralizing antibody, IgG control and JAK2/STAT3 pathway blocker AG-490. Blood pressure (BP), serum creatinine (Scr), urinary albumin/creatinine ratio (UACR) and renal histopathology were measured; renal Th22 cells proportion were detected by flow cytometry; inflammatory factors were evaluated by ELISA, and JAK2/STAT3, fibrotic related factors were detected by western blot.

Results

1. Expression of IL-22/IL-22R and infiltrated Th22 cells proportion in kidney were elevated in Ang II-induced hypertensive mice; 2. Treatment with rIL-22 resulted in further elevated BP, UACR, renal Th22 and IL-22, renal pathological damage and inflammatory responses, and increased renal fibrosis and JAK2/STAT3 pathway activation, compared to hypertensive mice treated by Ang II alone; 3. In contrast, treatment with the anti-IL-22 antibody decreased BP, UACR, renal Th22 and IL-22 and renal pathological damage, also attenuated renal inflammation, fibrosis and JAK2/STAT3 pathway activation.

Conclusion

1. Recombinant IL-22 may activate JAK2/STAT3 pathway by binding to IL-22R in kidney, increase BP, aggravate immune inflammation and renal fibrosis in Ang II infused hypertensive mice; 2. Anti-IL-22 neutralizing antibody can reduce BP, inflammation and renal fibrosis in hypertensive kidney damage, which may be through inhibiting the activation of JAK2/STAT3 pathway.

Funding

  • Government Support - Non-U.S.