The Effect of Aerobic Exercise on Renal Fibrosis in Diabetic Rats through the Modulation of miR-21/miR-29

This study aimed to investigate the development of renal fibrosis in T2DM (type 2 diabetes mellitus) rats and the effects of aerobic exercise intervention. Furthermore, it explored the mechanism by which miR- 21 and miR-29 regulate the TGF-β1/Smad3 signaling pathway to ameliorate diabetic renal fibrosis in response to aerobic exercise. Fifty rats were randomly assigned, with ten serving as the NC (normal control) group and forty used to establish the DM (T2DM model). The modeling procedure consisted of a 5-week high-fat diet followed by a low-dose intraperitoneal injection of STZ (streptozotocin). Successfully modeled diabetic rats were then randomly divided into two groups: the DC (diabetic control) group and the DE (diabetic exercise) group. The DE group un- derwent an 8-week aerobic exercise program, with sessions lasting 60 min conducted six times per week. Urine and blood biochemical parameters were detected in all groups. The degree of renal fibrosis was observed using HE and Masson staining. The protein expression levels of TGF-β1, Smad3, α-SMA, and collagen I were determined by Western blot analysis, and the expression levels of miR-21 and miR-29 were measured by RT-qPCR. Compared with the NC group, rats in the DC group exhibited significant body mass loss at weeks 6 and 8 (P<0.05, P<0.01). Conversely, the DE group showed an increasing trend in body mass compared with the DC group, although this did not reach statistical significance. Regarding metabolic parameters, the DC group displayed significantly elevated levels of FBG, HOMA-IR, HbA1c, TC, LDL, TG, urinary protein, urinary urea nitrogen, and urinary creatinine compared with the NC group (P<0.05, P<0.01). Concurrently, INS and HDL levels were significantly reduced (P<0.05) (P<0.01). Aerobic exercise intervention in the DE group significantly ameliorated these alterations, resulting in marked reduction in FBG, HbA1c, TC, LDL, TG, urinary protein, urinary urea nitrogen, and urinary creatinine (P<0.05, P<0.01), a significant increase in INS (P<0.05), and a non-significant upward trend in HDL levels compared with the DC group. Histological analysis via HE staining revealed irregular glomerular morphology and vacuolar degeneration of renal tubular epithelial cells in the DC group, both of which were ameliorated in the DE group. Masson staining demonstrated a significant increase in collagen deposition (blue-stained area) in the DC group compared with the NC group (P<0.01), which was substantially attenuated in the DE group (P<0.01). Consistent with these findings, Western blot analysis indicated that the expression levels of the fibrosis markers α-SMA and collagen I were significantly upregulated in the renal tissues of the DC group relative to the NC group (P<0.05). Compared with the DC group, the DE group showed a significant downregulation in collagen I expression (P<0.05), while α-SMA expression exhibited a decreasing trend that did not reach statistical significance. Renal tissues from the DC group showed a pronounced upregulation of miR-21 (P<0.01) and a significant downregulation of miR-29 (P<0.05) compared with the NC group. Exercise intervention in the DE group reversed these changes, resulting in a significant reduction in miR-21 (P<0.05) and a non-significant increasing trend in miR-29 compared with the DC group. Correspondingly, the protein expression levels of the downstream targets TGF-β1 and Smad3 were signifi- cantly higher in the DC group than in the NC group (P<0.01). This activation was significantly suppressed in the DE group, with both proteins showing markedly decreased expression levels (P<0.05). An 8-week regimen of aerobic exercise ameliorates renal fibrosis in T2DM rats. The underlying mechanism appears to involve the downregulation of miR-21 and the upregulation of miR-29, which consequently inhibits the TGF-β1/Smad3 signaling pathway.

CSTR: 32200.14.cjcb.2026.04.0013