Rheological Influence Upon the Glomerular Podocyte and Resultant Mechanotransduction

Abstract

The glomerular podocyte is exposed to numerous mechanical forces as a constituent of the glomerular filtration apparatus. This includes fluid shear stress (FSS) displaced upon the podocytic foot process's apical, lateral, and basal surfaces. Even in the face of continuous flow the podocyte is capable of contributing to physiologic filtration, however with pathologic levels of hyperfiltration there is increased FSS placed upon the cell. The mechanisms by which the podocyte detects and responds to FSS are topics of recent investigations, with the aim to clarify the way these cells are injured and/or adapt in times of hyperfiltration and disease states. As the pathogenesis of numerous glomerulopathies is contingent on the status of the podocyte, understanding the manner that these cells can be modified by FSS is essential. Likewise, determination of the effect of such mechanical forces upon other resident cells of the renal corpuscle would reveal the contribution of FSS in the progression of glomerular diseases. The biochemical manner in which podocytes sense and respond to FSS, that is mechanotransduction, will be discussed.

Hyperfiltration-associated biomechanical forces in glomerular injury and response: Potential role for eicosanoids

“…These findings are in accordance with previously reported increase in albumin permeability in glomeruli incubated with PGE 2 [69]. Recent updates show that COX2-PGE 2 -EP 2 axis with the activation of AKT- GSK3β- β catenin and c-src-PLD-mTOR are considered mediators of the effects of FFSS [61]. …”

“…Other investigators have also emphasized the significance of shear stress in damage and loss of podocytes [59,61]. It is noteworthy that children born with a solitary kidney generally develop hypertension, albuminuria and/or decreased eGFR during late adolescence/young adulthood suggesting that FFSS drives the early loss of glomerular function in these children.…”

Increased podocyturia in pregnant women compared to non‐pregnant women

“…Thus, physiological hyperfiltration occurs even in normotensive pregnancies . The glomerular podocytes are vulnerable to a stress of hyperfiltraton . This may explain the accelerated detachment of podocytes and cells expressing AQP2‐mRNA from the kidney seen in this study.…”

“…The podocytes are glomerular epithelial cells, located at the outermost layer of the glomerular basement membrane, the foot processes of which form tight interdigitating networks that regulate the filtration of circulating plasma proteins from the capillary lumen into Bowman's space . The podocytes detach from the glomerular basement membrane under various stimuli including hyperfiltration and hypertension, and are excreted in the urine, resulting in podocyturia . Podocytes are present in the urine of healthy subjects without renal disease, although the number of urine podocytes is small, i.e., less than one podocyte per milligram of creatinine vs. up to 388 podocytes per milligram of creatinine in patients with active glomerular disease .…”

Rapamycin Induces Autophagy and Reduces the Apoptosis of Podocytes Under a Stimulated Condition of Immunoglobulin A Nephropathy

“…Thus, maintenance of podocyte health and function is important for the glomerular filtration in the kidney. Any significant damage to the podocytes such as apoptosis [6] and rheological influence [7] may induce irreversible glomerular injury [8]. A previous study [9] using podocyte-specific transgenic mice with deletion of the Atg5 gene eloquently demonstrated the importance of autophagy to podocytes.…”