Epithelial–mesenchymal Transition of Glomerular Podocytes: Implications in Proteinuria

Abstract

The kidneys play an essential role in filtration of blood plasma, regulation of water, electrolyte, and acid/base balance of the body, and thus maintain overall homeostasis. The glomerular filtration barrier serves as a size, shape, and charge barrier to ensue glomerular permselectivity, so that kidneys excrete almost protein-free urine. Podocytes are glomerular visceral epithelial cells and significantly contribute to the glomerular permeability owing to their unique structure and specialized function. Nevertheless, podocytes are susceptible to various insults, including altered metabolites, aberrant signaling molecules, and mutations to critical proteins that otherwise ensue normal function. Podocyte injury is a predominant indicator of several glomerular diseases that are manifested by proteinuria. Epithelial-mesenchymal transition (EMT) is considered as one of the responses of podocytes to the noxious stimuli, which consequently results in podocyte depletion and proteinuria. This review discusses the importance of podocytes in normal renal filtration and details the molecular and cellular events that lead to EMT of podocytes vis-à-vis impaired glomerular filtration.

Hypoxia induces ZEB2 in podocytes: Implications in the pathogenesis of proteinuria

“…Glomerular podocytes are instrumental to ensure glomerular permselectivity (Anil Kumar et al, ). It was reported that podocytes undergo EMT and such a glomerular injury with reduced podocyte count was associated with proteinuria (Chitra et al, ; Nishad, Nakuluri, Motrapu, & Pasupulati, ). To investigate whether the observed proteinuria and decreased podocyte count in rats exposed to hypoxia were owing to podocyte injury, we then investigated the effect of hypoxia on human immortalized podocytes.…”

“…Besides the loss of E‐ and P‐cadherin expression, several other proteins are also deregulated during EMT of podocytes including nephrin and podocin (Nishad et al, ). We found attenuated expression of ZO‐1 and increased expression of N‐cadherin, β‐catenin, and vimentin in rats exposed to hypoxia.…”

Understanding Glioblastoma Signaling, Heterogeneity, Invasiveness, and Drug Delivery Barriers

“…The EMT is a critical mechanism in physiological and pathological processes, such as embryogenesis, wound healing, and cancer development, enabling cells to transit from an epithelial to a mesenchymal state [ 59 ]. The literature defines three distinct EMT subtypes, each of which occurs in different biological circumstances and has a range of functional outcomes [ 60 , 61 ].…”

Epithelial-Mesenchymal Transition and its Role in Renal Fibrogenesis

“…Injury to the podocyte is an important cause of several glomerular diseases. One of the responses of podocytes to various injuries is EMT which results in depletion of these cells leading to heavy proteinuria [5]. The phenotypic switch seen in the podocytes closely resembles type II EMT [6].…”