Ghrelin attenuates UUO-induced renal fibrosis via attenuation of Nlrp3 inflammasome and endoplasmic reticulum stress

American Journal of Translational Research

Min Yang¹  Lilu Ling² 

[1] Division of Nephrology, Shanghai Ninth Peoples Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai 200011, China;Division of Nephrology, The Fifth Peoples Hospital of Shanghai, Fudan University, 128 Ruili Road, Shanghai 200240, China

关键词: Ghrelin;    renal fibrosis;    NLRP3 inflammasome;    endoplasmic reticulum stress;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Background/aims: All chronic kidney disease (CKD) can eventually develop into renal fibrosis. We explored the renoprotective effects of a gastric peptide, ghrelin, and investigated whether endoplasmic reticulum stress (ERS) and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome mediate the protective effect of ghrelin in unilateral ureteral obstruction (UUO). Methods: Male C57BL/6J mice were divided into vehicle- or ghrelin-treated sham-operated groups and vehicle- or ghrelin-treated UUO groups. The kidneys were harvested on postoperative day 14. Renal fibrosis was evaluated by periodic acid-Schiff, Masson trichrome, and immunohistochemical (IHC) staining. To assess renal fibrosis, α-smooth muscle actin and type I collagen were detected. NLRP3 inflammasome and ERS activation were also detected via western blotting. The effect of ghrelin on cultured renal cells was further confirmed in HK-2 cells. Results: Compared with the sham mice, UUO mice developed obvious renal fibrosis; pathological and IHC staining showed increased matrix accumulation and elevated ERS, NLRP3 inflammasome was activated both in vivo and in vitro. Ghrelin significantly attenuated collagen fibril accumulation and apoptosis by reducing NLRP3 inflammasome activation and ERS in obstructed kidneys. Conclusions: Ghrelin may attenuate UUO-induced renal fibrosis by inhibiting the NLRP3 inflammasome and ERS in vivo. Therefore, ghrelin might be an effective strategy for preventing CKD.

【 授权许可】

CC BY-NC