The preventive effects of exercise on renal dysfunction in D-galactose treated rats: the role of miR-296-5p and SGLT2.

Purpose: The prevalence of kidney diseases increases with diabetes and aging. Alterations in sodium-glucose transporters-2 (SGLT2) levels in the proximal tubule are associated with diabetes. This study evaluated effects of moderate-intensity endurance training (MIET) and high-intensity interval training (HIIT) on miR-296-5p expression, which acts as an upstream regulator of SGLT2 mRNA translation, as well as SGLT2 mRNA and protein levels in the kidney tissue of male Wistar rats during aging progression.

Methods: Concurrently with D-galactose (D-gal) injection, rats in the exercise groups underwent either MIET or HIIT. Histopathological indices and fibrosis were assessed using H&E and Masson's trichrome staining in six groups: CTL, CTL + MIET, CTL + HIIT, D-gal, D-gal + MIET, and D-gal + HIIT. The expression levels of miR-296-5p and SGLT2 mRNA were quantified by real-time PCR, while SGLT2 protein expression was determined via western blot analysis. Serum levels of creatinine, BUN, and glucose were determined via photometric methods.

Results: Both MIET and HIIT reduced glomerulosclerosis in D-gal-treated rats. Expression of miR-296-5p increased in both CTL and D-gal groups in response to MIET and HIIT. SGLT2 protein levels were elevated in the D-gal group compared to CTL controls. Both MIET and HIIT decreased SGLT2 protein levels in CTL and D-gal groups. Moreover, HIIT normalized serum creatinine and BUN levels in D-gal-treated animals.

Conclusion: MIET and HIIT modulate SGLT2 mRNA expression and protein levels by upregulating miR-296-5p. The reduction in SGLT2 levels is associated with decreased glucose uptake and improved kidney structure and function.