Th22/IL-22激活JAK2/STAT3信号促进高血压肾间质纤维化发生机制

CD4+T cells and the secreted inflammatory cytokines contribute to the progress of hypertensive renal interstitial fibrosis. In our previous studies, we found that the expression of Th22 cells and its effect factor IL-22 increased significantly in rat kidney of hypertensive renal damage, and were positively correlated with renal pathological damage. It is reported that IL-22 binds to its receptors and activates the JAK2/STAT3 pathway. Therefore, we hypothesize that Th22 cells may activate the JAK2/STAT3 pathway to promote hypertensive renal interstitial fibrosis via the secretion of IL-22. This study intends to carry out the following work: (1) Establish a rat model of hypertensive renal damage, and use the intervention of enhancing or inhibiting the effect of IL-22, and JAK2 channel blockers respectively, to verify the relationship among Th22/IL-22, JAK2/STAT3 and renal interstitial fibrosis; (2) Proximal renal tubular epithelial cells stimulated by angiotensin II are co-cultured with differentiated Th22 cells, and treated with the intervention such as JAK2 channel blockers. This study will clarify whether Th22/IL-22 are involved in hypertensive renal interstitial fibrosis through JAK2/STAT3 pathway, and find new therapeutic targets for hypertensive renal interstitial fibrosis.

CD4+T细胞及其分泌的炎症因子参与了高血压肾间质纤维化的进展。我们发现，高血压肾损害大鼠肾组织Th22细胞及其效应因子IL-22表达明显升高，与肾脏病理损伤呈正相关。研究报道，IL-22与其受体结合可激活JAK2/STAT3信号通路。据此，我们推测Th22细胞可能通过分泌IL-22，激活JAK2/STAT3通路促进高血压肾间质纤维化发生。本研究拟开展以下工作：（1）建立高血压肾损害大鼠模型，用增强或抑制IL-22效应、JAK2通路阻断剂干预，明确Th22/IL-22、JAK2/STAT3与肾间质纤维化的关系；（2）用血管紧张素II干预近端肾小管上皮细胞，将诱导分化的Th22细胞与其共培养，并使用JAK2通路阻断剂等进行干预，明确Th22/IL-22能否通过JAK2/STAT3通路参与高血压肾间质纤维化进展，为其防治提供新的作用靶点。

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