Exercise alleviates renal interstitial fibrosis by ameliorating the Sirt1-mediated TGF-β1/Smad3 pathway in T2DM mice.

BACKGROUND: Renal interstitial fibrosis is the pathophysiological basis of T2DM. Exercise appears to improve kidney interstitial fibrosis in T2DM, in which Sirt1 is a critical regulator. However, the role of Sirt1 in mediating exercise on renal tissue, as well as its mechanism remains unknown.

METHODS: T2DM mouse models were created using a high-fat diet mixed with streptozotocin, followed by 8 weeks of treadmill exercise and niacinamide (Sirt1 inhibitor) intervention. Kits for detecting biochemical indices of renal function were used. The pathological appearance and severity of renal tissue were examined using HE, Masson, and immunohistochemical staining. The mRNA and protein expression of relevant signaling pathway factors were determined to use RT-PCR and Western blotting.

RESULTS: T2DM can promote renal interstitial fibrosis, increase KI, SCr, BUN and 24h UTP, and cause pathological changes in renal tissue and affect renal function. After 8 weeks of exercise intervention, the biochemical indicators in the kidney of T2DM mice were decreased, Sirt1 expression was increased, the expression of TGF-β1, Smad3, COL1 and COL3 were decreased, and the renal interstitial fibrosis, renal tissue structural lesions and renal function were improved. However, after the nicotinamide intervention, renal interstitial fibrosis of T2DM mice was aggravated, and the improvement effect of exercise on renal interstitial fibrosis of T2DM mice was abolished.

CONCLUSION: The up-regulation of Sirt1 expression by exercise can inhibit the TGF-β1/Smad3 pathway, thereby inhibiting the expression and deposition of COL1 and COL3 in renal interstitium, thereby improving renal interstitial fibrosis in T2DM.