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.
| Original language | English |
|---|---|
| Pages (from-to) | 1769-1778 |
| Number of pages | 10 |
| Journal | American Journal of Pathology |
| Volume | 183 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Dec 2013 |
Fingerprint
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Nature and mediators of parietal epithelial cell activation in glomerulonephritides of human and rat. / Rizzo, Paola; Perico, Norberto; Gagliardini, Elena; Novelli, Rubina; Alison, Malcolm R.; Remuzzi, Giuseppe; Benigni, Ariela.
In: American Journal of Pathology, Vol. 183, No. 6, 12.2013, p. 1769-1778.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nature and mediators of parietal epithelial cell activation in glomerulonephritides of human and rat
AU - Rizzo, Paola
AU - Perico, Norberto
AU - Gagliardini, Elena
AU - Novelli, Rubina
AU - Alison, Malcolm R.
AU - Remuzzi, Giuseppe
AU - Benigni, Ariela
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84888226717&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888226717&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2013.08.008
DO - 10.1016/j.ajpath.2013.08.008
M3 - Article
C2 - 24095923
AN - SCOPUS:84888226717
VL - 183
SP - 1769
EP - 1778
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 6
ER -