Fang Zhang; Qiong Guo; Gulnigar Mamat; Yating Tian; Qiuyu Wang; Boxiang Zhang & Tian Li

Marein is a flavonoid compound that reduces blood glucose and lipids and has a protective effect in diabetes. However, the effect and mechanism(s) of marein on renal endothelial–mesenchymal transition in diabetic kidney disease (DKD) have not been elucidated. In this study, single-cell sequencing data on DKD were analyzed using a bioinformation method, and the data underwent reduced dimension clustering. It was found that endothelial cells could be divided into five subclusters. The developmental sequence of the subclusters was 0, 1, 4, 2, and 3, of which subcluster 3 had the most interstitial phenotype.The expression of mesenchymal marker protein:Vimentin(VIM), Fibronectin(FN1), and fibroblast growth factor receptor 1 (FGFR1) increased with the conversion of subclusters. In db/db mice aged 13–14 weeks, which develop DKD complications after 8–12 weeks of age, marein reduced blood levels of glucose, creatinine, and urea nitrogen, improved structural damage in kidney tissue, and reduced collagen deposition and the expression of FN1 and VIM. Marein also up-regulated autophagy marker:Light chain 3II/I(LC3II/I) and decreased FGFR1 expression in renal tissue. In an endothelial–mesenchymal transition model, a high glucose level induced a phenotypic change in human umbilical vein endothelial cells. Marein decreased endothelial cell migration, improved endothelial cell morphology, and decreased the expression of VIM and FN1. The use of the FGFR1 inhibitor, AZD4547, and autophagy inhibitor, 3-Methyladenine(3-MA), further demonstrated the inhibitory effect of marein on high glucose–induced endothelial–mesenchymal transition by reducing FGFR1 expression and up-regulating the autophagy marker protein, LC3II/I. In conclusion, this study suggests that marein has a protective effect on renal endothelial– mesenchymal transition in DKD, which may be mediated by inducing autophagy and down-regulating FGFR1 expression.

KEY WORDS: Endothlial-mesenchymal transition; Marein; Diabetic kidney disease; FGFR1; Autophagy.

ZHANG, F.; GUO, Q.; MAMAT, G.; TIAN, Y.; WANG, Q.; ZHANG, B. & LI, T. The role of marein during endothelial–mesenchymal transition in diabetic kidney disease. Int. J. Morphol., 42(4):1080-1095, 2024.