Suppression of ER-associated degradation by intraglomerular crosstalk between mesangial cells and podocytes causes podocyte injury in diabetic kidney disease

摘要

Introduction: Mesangial lesions and podocyte injury are essential manifestations of the progression of diabetic kidney disease (DKD). Although cross-communication between mesangial cells (MCs) and podocytes has recently been suggested by the results of single-nucleus RNA-sequencing analyses, the molecular mechanisms and role in disease progression remain elusive. Furthermore, our cDNA microarray data of diabetic mouse glomeruli suggested the involvement of endo- plasmic reticulum (ER) stress in DKD pathophysiology. Thus, we hy- pothesized that the cross-communication between MCs and podocytes may affect the ER stress responses of these cells and thereby participate in the progression of DKD, especially in podocyte injury. In this study, we aimed to clarify the role of this cellular crosstalk in podocyte injury under diabetic conditions.