Bowman's capsule parietal epithelial cell activation occurs in several human proliferative glomerulonephritides. The cellular composition of the resulting hyperplastic lesions is controversial, although a population of CD133+CD24+ progenitor cells has been proposed to be a major constituent. Mediator(s) involved in proliferation and migration of progenitor cells into the Bowman's space have been poorly explored. In a series of 36 renal biopsies of patients with proliferative and nonproliferative glomerulopathies, dysregulated CD133+CD24+ progenitor cells of the Bowman's capsule invade the glomerular tuft exclusively in proliferative disorders. Up-regulation of the CXCR4 chemokine receptor on progenitor cells was accompanied by high expression of its ligand, SDF-1, in podocytes. Parietal epithelial cell proliferation might be sustained by increased expression of the angiotensin II (Ang II) type-1 (AT1) receptor. Similar changes of CXCR4, SDF-1, and AT1 receptor expression were found in Munich Wistar Frömter rats with proliferative glomerulonephritis. Moreover, an angiotensin-converting enzyme inhibitor normalized CXCR4 and AT1 receptor expression on progenitors concomitant with regression of crescentic lesions in a patient with crescentic glomerulonephritis. These results suggest that glomerular hyperplastic lesions derive from the proliferation and migration of renal progenitors in response to injured podocytes. The Ang II/AT1 receptor pathway may participate, together with SDF-1/CXCR4 axis, to the dysregulated response of renal precursors. Thus, targeting the Ang II/AT1 receptor/CXCR4 pathways may be beneficial in severe forms of glomerular proliferative disorders.

Nature and mediators of parietal epithelial cell activation in glomerulonephritides of human and rat / P. Rizzo, N. Perico, E. Gagliardini, R. Novelli, M.R. Alison, G. Remuzzi, A. Benigni. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 183:6(2013 Dec), pp. 1769-1778. [10.1016/j.ajpath.2013.08.008]

Nature and mediators of parietal epithelial cell activation in glomerulonephritides of human and rat

G. Remuzzi
Penultimo
;
2013

Abstract

Bowman's capsule parietal epithelial cell activation occurs in several human proliferative glomerulonephritides. The cellular composition of the resulting hyperplastic lesions is controversial, although a population of CD133+CD24+ progenitor cells has been proposed to be a major constituent. Mediator(s) involved in proliferation and migration of progenitor cells into the Bowman's space have been poorly explored. In a series of 36 renal biopsies of patients with proliferative and nonproliferative glomerulopathies, dysregulated CD133+CD24+ progenitor cells of the Bowman's capsule invade the glomerular tuft exclusively in proliferative disorders. Up-regulation of the CXCR4 chemokine receptor on progenitor cells was accompanied by high expression of its ligand, SDF-1, in podocytes. Parietal epithelial cell proliferation might be sustained by increased expression of the angiotensin II (Ang II) type-1 (AT1) receptor. Similar changes of CXCR4, SDF-1, and AT1 receptor expression were found in Munich Wistar Frömter rats with proliferative glomerulonephritis. Moreover, an angiotensin-converting enzyme inhibitor normalized CXCR4 and AT1 receptor expression on progenitors concomitant with regression of crescentic lesions in a patient with crescentic glomerulonephritis. These results suggest that glomerular hyperplastic lesions derive from the proliferation and migration of renal progenitors in response to injured podocytes. The Ang II/AT1 receptor pathway may participate, together with SDF-1/CXCR4 axis, to the dysregulated response of renal precursors. Thus, targeting the Ang II/AT1 receptor/CXCR4 pathways may be beneficial in severe forms of glomerular proliferative disorders.
Adult; Aged; Aged, 80 and over; Animals; Chemokine CXCL12; Female; Humans; Inflammation Mediators; Male; Middle Aged; Peptidyl-Dipeptidase A; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptors, CXCR4; Cell Proliferation; Epithelial Cells; Glomerular Mesangium; Glomerulonephritis; Stem Cells; 2734
Settore MED/14 - Nefrologia
dic-2013
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/329619
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