The effect of intravenous injection of ckit + cells on pulmonary fibrosis through SIRT-1 / TFGβ / SMAD3 signaling pathway and inflammatory cytokines of type 2 diabetic male rats

Abstract

Pulmonary fibrosis caused by hyperglycemia increases the mortality rate of diabetic patients. It has been found that fibroblast growth factor (TFG-β) has a special role in the pathogenesis of diabetic lung. Considering the therapeutic potential of c-kit+ stem cells, in this study the possible antifibrotic effect of c-kit+ stem cell injection on the SIRT-1/TFGβ/SMAD3 pathway and inflammatory cytokines and fibrosis rate was studied in the lungs of diabetic rats. Methods: Forty-eight male rats were randomly divided into 4 groups: 1) Control group (C), received normal saline solution intravenously. 2) Diabetic group (D), diabetic animals that received normal saline solution intravenously. 3) diabetic group + c-kit+ cells (D+c-kit⁺), received one million c-kit⁺ cells intravenously. 4) Diabetic group + c-kit- cells (D+ckit -), received one million c-kit cells intravenously. Type 2 diabetes was induced by a high-fat diet followed by intraperitoneal injection of streptozotocin. 60 days after cell therapy, the right lung was used to measure IL-1ß, Col3, Col1A, TGFβ, Smad3, P21, and SIRT-1 proteins, and the left lung was used to investigate fibrosis. Results: Type 2 diabetes in the rat model caused lung tissue fibrosis, and increased inflammatory marker IL-1ß, as well as increased Col3, Col1A, TGFβ, Smad3, P21 proteins and decreased SIRT-1 protein expression. While intravenous injection of c-kit+ cells could modulate pulmonary fibrosis and the levels of these factors.