Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction

M. J. Butt, Alice F Tarantal, D. F. Jimenez, D. G. Matsell

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Renal interstitial fibrosis contributes to the progression of most chronic kidney diseases and is an important pathologic feature of urinary tract obstruction. To study the origin of this fibrosis, we used a fetal non-human primate model of unilateral ureteric obstruction focusing on the role of medullary collecting duct (CD) changes. Obstruction at 70 days gestation (full term approximately 165 days) results in cystic dysplasia with significant medullary changes including loss of the epithelial phenotype and gain of a mesenchymal phenotype. These changes were associated with disruption of the epithelial basement membrane and concomitant migration of transitioning cells presumed responsible for the observed peritubular collars of fibrous tissue. There was an abundance of cells that co-expressed the intercalated cell marker carbonic anhydrase II and smooth muscle actin. These cells migrated through the basement membrane and were significantly reduced in obstructed ducts with peritubular collars. Our studies suggest that fetal urinary tract obstruction results in a CD epithelial-mesenchymal transition contributing to the interstitial changes associated with poor prognosis. This seems restricted to the intercalated cells, which contribute to the expansion of the principal cell population and the formation of peritubular collars, but are depleted in progressive injury.

Original languageEnglish (US)
Pages (from-to)936-944
Number of pages9
JournalKidney International
Volume72
Issue number8
DOIs
StatePublished - Oct 2007

Fingerprint

Epithelial-Mesenchymal Transition
Urinary Tract
Basement Membrane
Fibrosis
Carbonic Anhydrase II
Phenotype
Chronic Renal Insufficiency
Primates
Cell Movement
Smooth Muscle
Actins
Kidney
Pregnancy
Wounds and Injuries
Population

Keywords

  • Collecting ducts
  • Fibrosis
  • Obstructive nephropathy
  • Renal development

ASJC Scopus subject areas

  • Nephrology

Cite this

Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction. / Butt, M. J.; Tarantal, Alice F; Jimenez, D. F.; Matsell, D. G.

In: Kidney International, Vol. 72, No. 8, 10.2007, p. 936-944.

Research output: Contribution to journalArticle

Butt, M. J. ; Tarantal, Alice F ; Jimenez, D. F. ; Matsell, D. G. / Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction. In: Kidney International. 2007 ; Vol. 72, No. 8. pp. 936-944.
@article{33b235513f184ce6846378d9422ecd4b,
title = "Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction",
abstract = "Renal interstitial fibrosis contributes to the progression of most chronic kidney diseases and is an important pathologic feature of urinary tract obstruction. To study the origin of this fibrosis, we used a fetal non-human primate model of unilateral ureteric obstruction focusing on the role of medullary collecting duct (CD) changes. Obstruction at 70 days gestation (full term approximately 165 days) results in cystic dysplasia with significant medullary changes including loss of the epithelial phenotype and gain of a mesenchymal phenotype. These changes were associated with disruption of the epithelial basement membrane and concomitant migration of transitioning cells presumed responsible for the observed peritubular collars of fibrous tissue. There was an abundance of cells that co-expressed the intercalated cell marker carbonic anhydrase II and smooth muscle actin. These cells migrated through the basement membrane and were significantly reduced in obstructed ducts with peritubular collars. Our studies suggest that fetal urinary tract obstruction results in a CD epithelial-mesenchymal transition contributing to the interstitial changes associated with poor prognosis. This seems restricted to the intercalated cells, which contribute to the expansion of the principal cell population and the formation of peritubular collars, but are depleted in progressive injury.",
keywords = "Collecting ducts, Fibrosis, Obstructive nephropathy, Renal development",
author = "Butt, {M. J.} and Tarantal, {Alice F} and Jimenez, {D. F.} and Matsell, {D. G.}",
year = "2007",
month = "10",
doi = "10.1038/sj.ki.5002457",
language = "English (US)",
volume = "72",
pages = "936--944",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction

AU - Butt, M. J.

AU - Tarantal, Alice F

AU - Jimenez, D. F.

AU - Matsell, D. G.

PY - 2007/10

Y1 - 2007/10

N2 - Renal interstitial fibrosis contributes to the progression of most chronic kidney diseases and is an important pathologic feature of urinary tract obstruction. To study the origin of this fibrosis, we used a fetal non-human primate model of unilateral ureteric obstruction focusing on the role of medullary collecting duct (CD) changes. Obstruction at 70 days gestation (full term approximately 165 days) results in cystic dysplasia with significant medullary changes including loss of the epithelial phenotype and gain of a mesenchymal phenotype. These changes were associated with disruption of the epithelial basement membrane and concomitant migration of transitioning cells presumed responsible for the observed peritubular collars of fibrous tissue. There was an abundance of cells that co-expressed the intercalated cell marker carbonic anhydrase II and smooth muscle actin. These cells migrated through the basement membrane and were significantly reduced in obstructed ducts with peritubular collars. Our studies suggest that fetal urinary tract obstruction results in a CD epithelial-mesenchymal transition contributing to the interstitial changes associated with poor prognosis. This seems restricted to the intercalated cells, which contribute to the expansion of the principal cell population and the formation of peritubular collars, but are depleted in progressive injury.

AB - Renal interstitial fibrosis contributes to the progression of most chronic kidney diseases and is an important pathologic feature of urinary tract obstruction. To study the origin of this fibrosis, we used a fetal non-human primate model of unilateral ureteric obstruction focusing on the role of medullary collecting duct (CD) changes. Obstruction at 70 days gestation (full term approximately 165 days) results in cystic dysplasia with significant medullary changes including loss of the epithelial phenotype and gain of a mesenchymal phenotype. These changes were associated with disruption of the epithelial basement membrane and concomitant migration of transitioning cells presumed responsible for the observed peritubular collars of fibrous tissue. There was an abundance of cells that co-expressed the intercalated cell marker carbonic anhydrase II and smooth muscle actin. These cells migrated through the basement membrane and were significantly reduced in obstructed ducts with peritubular collars. Our studies suggest that fetal urinary tract obstruction results in a CD epithelial-mesenchymal transition contributing to the interstitial changes associated with poor prognosis. This seems restricted to the intercalated cells, which contribute to the expansion of the principal cell population and the formation of peritubular collars, but are depleted in progressive injury.

KW - Collecting ducts

KW - Fibrosis

KW - Obstructive nephropathy

KW - Renal development

UR - http://www.scopus.com/inward/record.url?scp=34948892919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34948892919&partnerID=8YFLogxK

U2 - 10.1038/sj.ki.5002457

DO - 10.1038/sj.ki.5002457

M3 - Article

C2 - 17667982

AN - SCOPUS:34948892919

VL - 72

SP - 936

EP - 944

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 8

ER -