Dynamic changes of podocytes caused by fibroblast growth factor 2 in culture

Eishin Yaoita,Hidehiko Fujinaka,Yutaka Yoshida,Masaaki Nameta

doi:10.1007/s00441-021-03511-x

Abstract

Fibroblast growth factor 2 (FGF2) augments podocyte injury, which induces glomerulosclerosis, although the mechanisms remain obscure. In this study, we investigated the effects of FGF2 on cultured podocytes with interdigitating cell processes in rats. After 48 h incubation with FGF2 dynamic changes in the shape of primary processes and cell bodies of podocytes resulted in the loss of interdigitation, which was clearly shown by time-lapse photography. FGF2 reduced the gene expressions of constituents of the slit diaphragm, inflections of intercellular junctions positive for nephrin, and the width of the intercellular space. Immunostaining for the proliferation marker Ki-67 was rarely seen and weakly stained in the control without FGF2, whereas intensely stained cells were frequently found in the presence of FGF2. Binucleation and cell division were also observed, although no significant increase in cell number was shown. An in vitro scratch assay revealed that FGF2 enhanced migration of podocytes. These findings show that FGF2 makes podocytes to transition from the quiescent state into the cell cycle and change their morphology due to enhanced motility, and that the culture system in this study is useful for analyzing the pathological changes of podocytes in vivo.

Highlights

Visceral glomerular epithelial cells in the kidney, which are referred to as podocytes, reside in a quiescent state and reveal no evidence of proliferation (Pabst and Sterzel 1983)
The effects of fibroblast growth factor 2 (FGF2) on podocytes were investigated in the culture
It was found that FGF2 caused significant changes in podocyte morphologies and gene expressions in a dose-dependent manner

Summary

Introduction

Visceral glomerular epithelial cells in the kidney, which are referred to as podocytes, reside in a quiescent state and reveal no evidence of proliferation (Pabst and Sterzel 1983). Podocytes interdigitate with each other in an elaborate morphology of cell bodies, primary processes, ridge-like prominences, and foot processes (Burghardt et al 2015; Ichimura et al 2015) They possess a unique intercellular junction called the slit diaphragm, which plays a crucial role in the glomerular filtration barrier. Injections of fibroblast growth factor 2 (FGF2) into rats for several weeks induce remarkable morphological changes that indicated mitosis and injury of podocytes (Floege et al 1995; Kriz et al 1995; Mazué et al 1993). These changes are followed by the development of widespread FSGS (Kriz et al 1995).

Methods

Results

Conclusion