Drugs to foster kidney regeneration in experimental animals and humans.
BACKGROUND
The incidence of kidney diseases is increasing worldwide and they are emerging as a major public health problem. Once mostly considered inexorable, renal disease progression can now be halted and lesions can even regress with drugs such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II type I receptor blockers, indicating the possibility of kidney repair.


CONCLUSIONS
The discovery of renal progenitor cells lining the Bowman capsule of adult rat and human kidneys has shed light on the mechanism of repair by ACEi. Parietal progenitors are a reservoir of cells that contribute to podocyte turnover in physiological conditions. In the early phases of renal disease these progenitors migrate chaotically and subsequently proliferate, accumulating in Bowman's space. The abnormal behavior of parietal progenitors is sustained by the activation of CXCR4 receptors in response to an increased production of the chemokine SDF-1 by podocytes activated by the inflammatory environment. Ang II, via the AT1 receptor, also contributes to progenitor cell proliferation. The CXCR4/SDF-1 and Ang II/AT1 receptor pathogenic pathways both pave the way for lesion formation and subsequent sclerosis. ACEi normalize the CXCR4 and AT1 receptor expression on progenitors, limiting their proliferation, concomitant with the regression of hyperplastic lesions in animals, and in a patient with crescentic glomerulopathy.


CONCLUSIONS
Understanding the molecular and cellular determinants of regeneration triggered by renoprotective drugs will reveal novel pathways that might be challenged or targeted by pharmacological therapy.
IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
Elena
E
Gagliardini
Ariela
A
Benigni
D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D050476:Bowman Capsule / Q000166:cytology; D054377:Chemokine CXCL12; D006801:Humans; D007668:Kidney / Q000502:physiology*; D050199:Podocytes / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000502:physiology; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D013234:Stem Cells / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D044140:Receptor, Angiotensin, Type 1; D019718:Receptors, CXCR4; D000804:Angiotensin II