Inhibiting angiotensin-converting enzyme promotes renal repair by modulating progenitor cell activation.
Independently of the initial insult, activation and accumulation of parietal progenitor cells within the Bowman's space is a peculiar feature of proliferative chronic kidney diseases. Clinical and experimental studies demonstrated that, in the presence of extensive renal damage, progenitor cells proliferate excessively in the failed attempt to replace the injured podocytes, contributing to the development of crescentic lesions. Inhibiting angiotensin-converting enzyme (ACE) halts crescent formation and promotes the restoration of normal glomerular architecture by limiting progenitor cell proliferation and migration towards the glomerular tuft. Among the mediators involved in the dysregulated response of renal precursors, the angiotensin II (ang II)/ang II type-1 (AT1) receptor/CXCR4 pathway have been demonstrated to be crucial in proliferative diseases. Understanding the mechanisms underlying the formation of crescentic lesions could be instrumental to developing new therapies, which can be more effective and more targeted to molecular mediators than the currently used cytotoxic agents.
IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
Paola
P
Rizzo
IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
Rubina
R
Novelli
IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy. Electronic address: ariela.benigni@marionegri.it.
Ariela
A
Benigni
IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy; Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
Giuseppe
G
Remuzzi
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000502:physiology* / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000503:physiopathology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A
ACE inhibitor; Angiotensin II; Crescents; Parietal epithelial cells; Renal progenitor cells; kidney regeneration