Objective: ELABELA (ELA), an endogenous ligand for apelin receptor (APJ), is decreased in plasma of DKD patients. The effects of ELA on relieving diabetic renal lesion have not been reported. This study was performed to explore the protective impact and potential mechanisms of ELA on DKD via β-arrestins.

Methods: Sixteen eight-week-old male db/db mice were randomly divided into diabetic nephropathy group (db/db group) and intervention group (db/db+ELA group) with administration of ELA (5mg ∙ kg-1 ∙ day-1) for 8 weeks. 8 age-matched male db/m mice were recognized as normal control group (db/m group). Both db/db and db/m group received equivalent normal saline injection for 8 weeks. Body weights and blood glucose levels were measured once a week. After 8 weeks, blood and urine samples were collected. Serum creatinine and urinary albumin to creatinine ration (UACR) were examined. The kidneys were taken after sacrificing mice. The morphology change of kidney tissues were assessed by HE and PAS staining. The expression of β-Arrestin1/2 was detected by immunohistochemistry. The levels of fibronectin (FN), collagen type IV (Col-IV) and β-arrestin1/2 in kidney tissues were examined by western blotting.

Results: (1) With the intervention of ELA, UACR, serum creatinine and the ratio of kidney weight to body weight of db/db mice were significantly decreased (P<0.05). (2) Compared with db/m mice, db/db mice exhibited renal tubular epithelial cells edema, decreased ratio of non-lumen area to total area, thickened basement membrane and increased glycogen accumulation, however, those pathological abnormality were mitigated by ELA. (3) The levels of FN, Col-IV and β-Arrestin-1/2 in db/db mice were higher than db/m mice, while ELA treatment suppressed the expression of FN, COL-IV and β-Arrestin-1/2 (P<0.05).

Conclusions: ELA may play a role in protection from diabetic kidney damage via down-regulating the expression of β-Arrestin-1/2 and inhibiting the secretion of extracellular matrix.


M. Shi: None. Y. Chen: None. H. Zhang: None.


National Natural Science Foundation of China (81700723)

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