Author:
Yang Fan,Wang Jiajia,Ju Tuoyu,Wang Shuwei,Qu Kaige,Song Zhengxun,Chen Yujuan,Wang Zuobin
Abstract
AbstractSmall extracellular vesicles (sEVs) participate in the pathological progression of high glucose (HG)-induced kidney injury, which is closely related to diabetic nephropathy. How sEVs specifically mediate the cell biomechanics underlying HG injury is unclear. Herein, we utilized a versatile atomic force microscope to determine the contributions of sEVs in HG-induced cellular injury. The sEVs extracted from the culture medium of human proximal tubule kidney (HK-2) cells treated by HG for 72 h (HG-induced sEVs) were verified and analyzed by multiple techniques, and the results indicated the effective production and the effect of dehydration on the shape of HG-induced sEVs. Further investigation on the morphologies of HK-2 cells treated by HG-induced sEVs showed that the surface roughness of the HK-2 cells increased, and their pseudopodia transitioned from lamellipodia to filopodia, with almost doubled mean pseudopodia length. Quantitative analysis of the mechanical responses of the cells revealed that the mean Young’s modulus increased by 26.2%, and the mean adhesion decreased by 36.8%. The indirect mediation of cellular biomechanics guided by HG-induced sEVs was evaluated by comparing it with previously studied direct HG injury. The HG-induced sEVs caused a greater reduction in cell adhesion and an increase in Young’s modulus compared with direct HG stimulation. This work suggested the ability of HG-induced sEVs to elicit specific biomechanical responses during HG injury, advancing the understanding of the injury mechanism caused by HG. The comparison of the cellular biomechanics between direct and indirect HG stimulations through HG-induced sEVs can be beneficial for the diagnosis and treatment of kidney injury.
Funder
National Natural Science Foundation Program of China
EU H2020 Program
Jilin Provincial Science and Technology Program
Jilin Provincial Education Department
“111” Project of China
Changli Nano Biotechnology
China Scholarship Council
Publisher
Springer Science and Business Media LLC
Subject
Industrial and Manufacturing Engineering,Mechanical Engineering,Materials Science (miscellaneous)