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Targeted Regulating of TGFBR1 Expression by Bone Marrow Mesenchymal Stem Cell-Derived Exosome Let-7a and its Mechanism in Diabetic Nephropathy Rats

Author(s): Zirui Pang, Xiaoxi Chen and Linbo Zhang*
Department of Endocrinology, Ankang Central Hospital, Ankang, Shaanxi Province 725000, 1Department of Nephrology, The First Hospital of Yulin, Yulin, Shaanxi Province 719000, China

Correspondence Address:
Linbo Zhang, Department of Nephrology, The First Hospital of Yulin, Yulin, Shaanxi Province 719000, China, E-mail:

To explore the renal protection mechanism of targeted regulating of transforming growth factor beta receptor type 1 expression by let-7a in diabetic nephropathy rats, diabetic nephropathy rats were created through high-sugar and high-fat diet combined with a small dose of streptozotocin. Normally reared rats were taken as control group. Diabetic nephropathy rats were divided into two groups, one group was treated with let-7a analogs group, and the other group was not treated (diabetic nephropathy group). Experimental results showed that diabetic nephropathy rats had symptoms such as increased dietary frequency, weight loss, proteinuria, and decreased creatinine clearance. After let-7a treatment, the proteinuria symptoms of rats in let-7a analogs group were notably improved, and the creatinine clearance rate increased. The expression level of collagen IV in let-7a analogs group was higher than that of the control, but the difference was not significant. The expression level of fibronectin increased significantly in the diabetic nephropathy group (p<0.05), and that of the let-7a analogs group was significantly lower than that of the diabetic nephropathy group (p<0.05). The immunofluorescence expression result was consistent with the expression trend detected by Western blot. Compared with the control, the expressions of transforming growth factor-beta 1, transforming growth factor beta receptor type 1, and mothers against decapentaplegic homolog 2 in the diabetic nephropathy group were evidently increased (p<0.05), and the expression of mothers against decapentaplegic homolog 7 decreased obviously (p<0.05). The protein expression level was consistent with the messenger ribonucleic acid expression result. In summary, by regulating the levels of collagen IV and fibronectin and targeting the transforming growth factor beta receptor type 1 pathway, let-7a inhibited extracellular matrix synthesis to protect kidney function in patients with diabetic nephropathy.

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