Basic Research
Protective effects of Elabela on kidney injury in db/db diabetic mice and its possible mechanism
Xu Yudi, Shi Min, Chen Juan, Gu Wensha, Weng Yaqin, Xu Wendong, Tan Dongjin, Zhang Hong
Published 2020-10-25
Cite as Chin J Endocrinol Metab, 2020, 36(10): 871-875. DOI: 10.3760/cma.j.cn311282-20200225-00098
Abstract
ObjectiveTo investigate the protective effects of Elabela(ELA) on the renal injury of db/db mice and its possible mechanism.
MethodsSixteen eight-week-old male db/db mice were intraperitoneally injected with ELA(5 mg·kg-1·day-1) or equivalent normal saline(n=8) for 8 weeks. Eight age-matched male db/m mice received equivalent normal saline injection as normal control. At the end of the experiment, blood and urine samples were obtained for HbA1C and urinary albumin/creatinine(ACR) measurements. Immunohistochemistry was used to observe the expression of ELA. Histopathological changes in kidney tissue were observed by HE staining and Masson staining. The levels of collagen type Ⅳ(Col-Ⅳ) and transforming growth factor-β1(TGF-β1) as well as Yes-associated protein(YAP) phosphorylation in kidney tissue were examined by western blot.
ResultsImmunohistochemistry results showed that ELA expression was decreased in the renal tissue of db/db mice as compared with that of db/m mice(P<0.05). After ELA treatment, ACR and blood pressure were markedly decreased in db/db mice(P<0.05), but without significant changes in the body weight and HbA1C. Renal tubular epithelial cells edema, basement membrane thickening, and increased collagen fiber in db/db were improved by ELA administration. Compared with db/m mice, the levels of TGF-β1 and Col-Ⅳ expression, as well as YAP phosphorylation were significantly increased in renal tissue of db/db mice(0.98±0.08vs 0.68±0.10, 1.10±0.14 vs 0.51±0.08, 3.38±0.72 vs 0.81±0.13, all P<0.05), which were down-regulated after ELA administration(0.80±0.06, 0.51±0.05, 2.21±0.22, allP<0.05).
ConclusionELA may improve the renal injury of db/db mice by regulating the signaling pathway of YAP, thereby delaying the development of diabetic nephropathy.
Key words:
Elabela; db/db mice; Diabetic nephropathy; Yes-associated protein; Transforming growth factor-β1
Contributor Information
Xu Yudi
Department of Endocrinology, Genetics and Metabolism, Huai′an First People′s Hospital Affiliated to Nanjing Medical University, Huai′an 223300, China
Shi Min
Department of Endocrinology, Genetics and Metabolism, Huai′an First People′s Hospital Affiliated to Nanjing Medical University, Huai′an 223300, China
Chen Juan
Department of Endocrinology, Genetics and Metabolism, Huai′an First People′s Hospital Affiliated to Nanjing Medical University, Huai′an 223300, China
Gu Wensha
Department of Endocrinology, Genetics and Metabolism, Huai′an First People′s Hospital Affiliated to Nanjing Medical University, Huai′an 223300, China
Weng Yaqin
Department of Endocrinology, Genetics and Metabolism, Huai′an First People′s Hospital Affiliated to Xuzhou Medical University, Huai′an 223300, China
Xu Wendong
Department of Endocrinology, Genetics and Metabolism, Huai′an First People′s Hospital Affiliated to Nanjing Medical University, Huai′an 223300, China
Tan Dongjin
Department of Endocrinology, Genetics and Metabolism, Huai′an First People′s Hospital Affiliated to Xuzhou Medical University, Huai′an 223300, China
Zhang Hong
Department of Endocrinology, Genetics and Metabolism, Huai′an First People′s Hospital Affiliated to Nanjing Medical University, Huai′an 223300, China
