Elabela alleviates diabetic kidney disease by regulating aquaporin 2 / 中华内分泌代谢杂志
Chinese Journal of Endocrinology and Metabolism
; (12): 651-657, 2022.
Article
Dans Zh
| WPRIM
| ID: wpr-957602
Responsable en Bibliothèque :
WPRO
ABSTRACT
Objective:
To assess the renal-protective effect of Elabela (Ela) on diabetic kidney disease (DKD), and explore its potential mechanism.Methods:
db/db mice were randomly divided into diabetic group and Ela intervention group, while db/m mice were taken as normal control group. The mice in the Ela intervention group were intraperitoneally injected with Ela-21 5 mg·kg -1·d -1 for 8 weeks. At the end of the experiment, urinary albumin/creatinine ratio (UACR) was measured. The renal pathological changes were observed by HE and PAS staining. The expression of aquaporin 2(AQP2) examined by immunohistochemistry. The level of collage Ⅳ(Col-Ⅳ) and AQP2 in renal tissue was analyzed by Western blot. The human renal tubular epithelial cells (HK-2) were incubated with high glucose medium and further interfered with apelin receptors (APJ)-siRNA. Western blot analysis was used to detect the effect of Ela intervention on Col-Ⅳ and AQP2 expression. Finally, to clarify the possible mechanism of Ela regulating AQP2, the interaction between Ela-induced APJ activation and arginine vasopressin (AVP)-evoked arginine vasopressin receptor 2 (AVPR2) activation was investigated by NanoBit ? technology.Results:
(1) Without affecting blood glucose and body weight, Ela intervention significantly reduced the UACR in db/db mice, and attenuate pathological changes of the kidney, as well as expression of Col-Ⅳ and AQP2. (2) Ela treatment could remarkably inhibit the high glucose-induced the expression of Col-Ⅳ and AQP2, which was reversed by interfering with APJ. (3) AVP-induced downstream β-Arrestin-2 signaling transduction via AVPR2 was obviously antagonized by interaction of Ela and APJ, further suggesting that the inhibitory effect of Ela on AQP2 may be related to antagonizing AVP/AVPR2 signaling.Conclusion:
Ela exerts renal protection by inhibiting the expression of AQP2 through APJ.
Texte intégral:
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Indice:
WPRIM
langue:
Zh
Texte intégral:
Chinese Journal of Endocrinology and Metabolism
Année:
2022
Type:
Article