The podocyte protease web: uncovering the gatekeepers of glomerular disease

American Journal of Physiology. Renal Physiology
Markus M RinschenRachelle E Koch

Abstract

Proteases regulate glomerular physiology. The last decade has revealed a multitude of podocyte proteases that govern the glomerular response to numerous chemical, mechanical, and metabolic cues. These proteases form a protein signaling web that integrates stress stimuli and serves as a key controller of the glomerular microenvironment. Both the extracellular and intracellular proteolytic networks are perturbed in focal segmental glomerulosclerosis, as well as hypertensive and diabetic nephropathy. Accordingly, the highly intertwined podocyte protease web is an integrative part of the podocyte's damage response. Novel mass spectrometry-based technologies will help to untangle this proteolytic network: functional readouts acquired from deep podocyte proteomics, single glomerular proteomics, and degradomics have exposed unanticipated protease activity in podocytes. Future efforts should characterize the interdependency and upstream regulation of key proteases, along with their role in promoting tissue heterogeneity in glomerular diseases. These efforts will not only illuminate the machinery of podocyte proteostasis but also reveal avenues for therapeutic intervention in the podocyte protease web.

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Citations

May 23, 2019·Current Hypertension Reports·Alexander StaruschenkoOleg Palygin
Aug 17, 2019·Journal of the American Society of Nephrology : JASN·Louise K FarmerGavin I Welsh
Jun 24, 2020·Molecular Biology Reports·Lichun YuShuzhen Sun
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Apr 18, 2021·Cell and Tissue Research·Fatih DemirMarkus M Rinschen
May 7, 2021·Journal of the American Society of Nephrology : JASN·Laith Farah Al-RabadiLaurence H Beck
Jun 3, 2021·Journal of the American Society of Nephrology : JASN·Favian A HatjeCatherine Meyer-Schwesinger

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