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Purpose <p>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.</p> Methods <p>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&amp;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.</p> Results <p>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.</p> Conclusion <p>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.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2025年9月29日

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  • Maryamossadat Mirtajaddini Goki,
  • Farzaneh Rostamzadeh,
  • Saeideh Jafarinejad-Farsangi,
  • Elham Jafari,
  • Zahra Soltani,
  • Sobhan Mansouri,
  • Hesam Askarimoghadam

摘要

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.

Graphical abstract