SB‐216763, a GSK‐3β inhibitor,protects against aldosterone‐induced cardiac,and renal injury by activating autophagy |
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| Authors: | Yi‐De Zhang Xiao‐Jun Ding Hou‐Yong Dai Wei‐Sheng Peng Nai‐Feng Guo Yuan Zhang Qiao‐Ling Zhou Xiao‐Lan Chen |
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| Affiliation: | 1. Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China;2. Department of Cardiology, Affiliated Danyang People's Hospital of Nantong University, Danyang, China;3. Department of Nephrology, Affiliated Xiangya Hospital of Central South University, Changsha, Hunan, China |
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| Abstract: | Cardiovascular and renal inflammation induced by Aldosterone (Aldo) plays a pivotal role in the pathogenesis of hypertension and renal fibrosis. GSK‐3β contributes to inflammatory cardiovascular and renal diseases, but its role in Aldo‐induced hypertension, and renal damage is not clear. In the present study, rats were treated with Aldo combined with SB‐216763 (a GSK‐3β inhibitor) for 4 weeks. Hemodynamic, cardiac, and renal parameters were assayed at the indicated time. Here we found that rats treated with Aldo presented cardiac and renal hypertrophy and dysfunction. Cardiac and renal expression levels of molecular markers attesting inflammation and fibrosis were increased by Aldo infusion, whereas the treatment of SB‐216763 reversed these alterations. SB‐216763 suppressed cardiac and renal inflammatory cytokines levels (TNF‐a, IL‐1β, and MCP‐1). Meanwhile, SB‐216763 increased the protein levels of LC3‐II in the cardiorenal tissues as well as p62 degradation, indicating that SB‐216763 induced autophagy activation in cardiac, and renal tissues. Importantly, inhibition of autophagy by 3‐MA attenuated the role of SB‐216763 in inhibiting perivascular fibrosis, and tubulointerstitial injury. These data suggest that SB‐216763 protected against Aldo‐induced cardiac and renal injury by activating autophagy, and might be a therapeutic option for salt‐sensitive hypertension and renal fibrosis. |
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| Keywords: | aldosterone autophagy cardiac and renal injury GSK‐3β inhibitor |
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