Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction

Kee Hwan Yoo, B. A. Thornhill, M. S. Forbes, C. M. Coleman, E. S. Marcinko, L. Liaw, R. L. Chevalier

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Congenital obstructive nephropathy is a major cause of renal insufficiency in children. Osteopontin (OPN) is a phosphoprotein produced by the kidney that mediates cell adhesion and migration. We investigated the role of OPN in the renal response to unilateral ureteral obstruction (UUO) in neonatal mice. OPN null mutant (-/-) and wild-type (+/+) mice were subjected to sham operation or UUO within the first 2 days of life. At 7 and 21 days of age, fibroblasts (fibroblast-specific protein (FSP)-1), myofibroblasts (α-smooth muscle actin (SMA)), and macrophages (F4/80) were identified by immunohistochemical staining. Apoptotic cells were detected by terminal deoxy transferase uridine triphosphate nick end-labeling technique and interstitial collagen by Masson trichrome or picrosirius red stain. Compared to sham-operated or contralateral kidneys, obstructed kidneys showed increases in all parameters by 7 days, with further increases by 21 days. After 21 days UUO, there was an increase in tubular and interstitial apoptosis in OPN -/- mice as compared to +/+ animals (P<0.05). However, FSP-1- and α-SMA-positive cells and collagen in the obstructed kidney were decreased in OPN -/- compared to +/+ mice (P<0.05), whereas the interstitial macrophage population did not differ between groups. We conclude that OPN plays a significant role in the recruitment and activation of interstitial fibroblasts to myofibroblasts in the progression of interstitial fibrosis in the developing hydronephrotic kidney. However, OPN also suppresses apoptosis. Future approaches to limit the progression of obstructive nephropathy in the developing kidney 1will require targeting of specific renal compartments.

Original languageEnglish
Pages (from-to)1735-1741
Number of pages7
JournalKidney International
Volume70
Issue number10
DOIs
Publication statusPublished - 2006 Nov 27

Fingerprint

Ureteral Obstruction
Osteopontin
Fibrosis
Apoptosis
Kidney
Myofibroblasts
Smooth Muscle
Actins
Collagen
Fibroblasts
Macrophages
Uridine Triphosphate
Phosphoproteins
Transferases
Cell Adhesion
Cell Movement
Renal Insufficiency
Coloring Agents
Staining and Labeling

Keywords

  • Apoptosis
  • Fibroblast
  • Hydronephrosis
  • Macrophage;Mouse
  • Myofibroblast

ASJC Scopus subject areas

  • Medicine(all)
  • Nephrology

Cite this

Yoo, K. H., Thornhill, B. A., Forbes, M. S., Coleman, C. M., Marcinko, E. S., Liaw, L., & Chevalier, R. L. (2006). Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction. Kidney International, 70(10), 1735-1741. https://doi.org/10.1038/sj.ki.5000357

Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction. / Yoo, Kee Hwan; Thornhill, B. A.; Forbes, M. S.; Coleman, C. M.; Marcinko, E. S.; Liaw, L.; Chevalier, R. L.

In: Kidney International, Vol. 70, No. 10, 27.11.2006, p. 1735-1741.

Research output: Contribution to journalArticle

Yoo, KH, Thornhill, BA, Forbes, MS, Coleman, CM, Marcinko, ES, Liaw, L & Chevalier, RL 2006, 'Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction', Kidney International, vol. 70, no. 10, pp. 1735-1741. https://doi.org/10.1038/sj.ki.5000357
Yoo, Kee Hwan ; Thornhill, B. A. ; Forbes, M. S. ; Coleman, C. M. ; Marcinko, E. S. ; Liaw, L. ; Chevalier, R. L. / Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction. In: Kidney International. 2006 ; Vol. 70, No. 10. pp. 1735-1741.
@article{9921e793d1c942169196cb4c6ee955b0,
title = "Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction",
abstract = "Congenital obstructive nephropathy is a major cause of renal insufficiency in children. Osteopontin (OPN) is a phosphoprotein produced by the kidney that mediates cell adhesion and migration. We investigated the role of OPN in the renal response to unilateral ureteral obstruction (UUO) in neonatal mice. OPN null mutant (-/-) and wild-type (+/+) mice were subjected to sham operation or UUO within the first 2 days of life. At 7 and 21 days of age, fibroblasts (fibroblast-specific protein (FSP)-1), myofibroblasts (α-smooth muscle actin (SMA)), and macrophages (F4/80) were identified by immunohistochemical staining. Apoptotic cells were detected by terminal deoxy transferase uridine triphosphate nick end-labeling technique and interstitial collagen by Masson trichrome or picrosirius red stain. Compared to sham-operated or contralateral kidneys, obstructed kidneys showed increases in all parameters by 7 days, with further increases by 21 days. After 21 days UUO, there was an increase in tubular and interstitial apoptosis in OPN -/- mice as compared to +/+ animals (P<0.05). However, FSP-1- and α-SMA-positive cells and collagen in the obstructed kidney were decreased in OPN -/- compared to +/+ mice (P<0.05), whereas the interstitial macrophage population did not differ between groups. We conclude that OPN plays a significant role in the recruitment and activation of interstitial fibroblasts to myofibroblasts in the progression of interstitial fibrosis in the developing hydronephrotic kidney. However, OPN also suppresses apoptosis. Future approaches to limit the progression of obstructive nephropathy in the developing kidney 1will require targeting of specific renal compartments.",
keywords = "Apoptosis, Fibroblast, Hydronephrosis, Macrophage;Mouse, Myofibroblast",
author = "Yoo, {Kee Hwan} and Thornhill, {B. A.} and Forbes, {M. S.} and Coleman, {C. M.} and Marcinko, {E. S.} and L. Liaw and Chevalier, {R. L.}",
year = "2006",
month = "11",
day = "27",
doi = "10.1038/sj.ki.5000357",
language = "English",
volume = "70",
pages = "1735--1741",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction

AU - Yoo, Kee Hwan

AU - Thornhill, B. A.

AU - Forbes, M. S.

AU - Coleman, C. M.

AU - Marcinko, E. S.

AU - Liaw, L.

AU - Chevalier, R. L.

PY - 2006/11/27

Y1 - 2006/11/27

N2 - Congenital obstructive nephropathy is a major cause of renal insufficiency in children. Osteopontin (OPN) is a phosphoprotein produced by the kidney that mediates cell adhesion and migration. We investigated the role of OPN in the renal response to unilateral ureteral obstruction (UUO) in neonatal mice. OPN null mutant (-/-) and wild-type (+/+) mice were subjected to sham operation or UUO within the first 2 days of life. At 7 and 21 days of age, fibroblasts (fibroblast-specific protein (FSP)-1), myofibroblasts (α-smooth muscle actin (SMA)), and macrophages (F4/80) were identified by immunohistochemical staining. Apoptotic cells were detected by terminal deoxy transferase uridine triphosphate nick end-labeling technique and interstitial collagen by Masson trichrome or picrosirius red stain. Compared to sham-operated or contralateral kidneys, obstructed kidneys showed increases in all parameters by 7 days, with further increases by 21 days. After 21 days UUO, there was an increase in tubular and interstitial apoptosis in OPN -/- mice as compared to +/+ animals (P<0.05). However, FSP-1- and α-SMA-positive cells and collagen in the obstructed kidney were decreased in OPN -/- compared to +/+ mice (P<0.05), whereas the interstitial macrophage population did not differ between groups. We conclude that OPN plays a significant role in the recruitment and activation of interstitial fibroblasts to myofibroblasts in the progression of interstitial fibrosis in the developing hydronephrotic kidney. However, OPN also suppresses apoptosis. Future approaches to limit the progression of obstructive nephropathy in the developing kidney 1will require targeting of specific renal compartments.

AB - Congenital obstructive nephropathy is a major cause of renal insufficiency in children. Osteopontin (OPN) is a phosphoprotein produced by the kidney that mediates cell adhesion and migration. We investigated the role of OPN in the renal response to unilateral ureteral obstruction (UUO) in neonatal mice. OPN null mutant (-/-) and wild-type (+/+) mice were subjected to sham operation or UUO within the first 2 days of life. At 7 and 21 days of age, fibroblasts (fibroblast-specific protein (FSP)-1), myofibroblasts (α-smooth muscle actin (SMA)), and macrophages (F4/80) were identified by immunohistochemical staining. Apoptotic cells were detected by terminal deoxy transferase uridine triphosphate nick end-labeling technique and interstitial collagen by Masson trichrome or picrosirius red stain. Compared to sham-operated or contralateral kidneys, obstructed kidneys showed increases in all parameters by 7 days, with further increases by 21 days. After 21 days UUO, there was an increase in tubular and interstitial apoptosis in OPN -/- mice as compared to +/+ animals (P<0.05). However, FSP-1- and α-SMA-positive cells and collagen in the obstructed kidney were decreased in OPN -/- compared to +/+ mice (P<0.05), whereas the interstitial macrophage population did not differ between groups. We conclude that OPN plays a significant role in the recruitment and activation of interstitial fibroblasts to myofibroblasts in the progression of interstitial fibrosis in the developing hydronephrotic kidney. However, OPN also suppresses apoptosis. Future approaches to limit the progression of obstructive nephropathy in the developing kidney 1will require targeting of specific renal compartments.

KW - Apoptosis

KW - Fibroblast

KW - Hydronephrosis

KW - Macrophage;Mouse

KW - Myofibroblast

UR - http://www.scopus.com/inward/record.url?scp=33750579753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750579753&partnerID=8YFLogxK

U2 - 10.1038/sj.ki.5000357

DO - 10.1038/sj.ki.5000357

M3 - Article

VL - 70

SP - 1735

EP - 1741

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 10

ER -