Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis

Jennifer L. Faulkner, Lisa M. Szcykalski, Fredyne Springer, Jeffrey L. Barnes

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

To determine whether previous renal injury accelerates the progression, of glomeralosclerosis and interstitial fibrosis, we examined the effect of treating rats with angiotensin II after Habu venom injury. After initiating disease, we examined the origin of interstitial myofibroblasts by locating α-smooth muscle actin (α-SMA)-positive and Na+,K+-ATPase- positive cells relative to interstitial space, tubular epithelial cells, the tubular basement membrane (TBM), and vascular structures. Tubular epithelial-mesenchymal transition was also assessed by examining TBM integrity and by using Texas Red (TR)-dextran in intravital tracking experiments. The staining of α-SMA-positive myofibroblasts dramatically increased in peritubular interstitial spaces 48 hours after Habu venom plus angiotensin II, particularly in and around perivascalar and periglomerular regions, while tubular epithelial cells were α-SMA-negative. Na+,K +-ATPase-positive and TR-dextran-labeled cells were restricted to the tubular epithelium and excluded from the interstitium. By 7 and 14 days, expanded interstitial space contained only α-SMA-positive myofibroblasts without TR-dextran endocytic particles. Epithelium of atrophic tubules containing TR-dextran remained confined by surrounding interstitium and myofibroblasts. These studies indicate that early expansion of α-SMA-positive cells in the interstitium and loss of tubular area occur via encroachment of interstitial myofibroblasts from perivascular into atrophic tubular spaces rather than via epithelial-mesenchymal transition and migration of tubular cells through the TBM into the interstitium.

Original languageEnglish (US)
Pages (from-to)1193-1205
Number of pages13
JournalAmerican Journal of Pathology
Volume167
Issue number5
StatePublished - Nov 2005

Fingerprint

Myofibroblasts
Angiotensin II
Dextrans
Fibrosis
Fibroblasts
Kidney
Trimeresurus
Basement Membrane
Epithelial-Mesenchymal Transition
Venoms
Epithelium
Epithelial Cells
Wounds and Injuries
Cell Movement
Smooth Muscle
Blood Vessels
Actins
Staining and Labeling
Texas red

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Faulkner, J. L., Szcykalski, L. M., Springer, F., & Barnes, J. L. (2005). Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis. American Journal of Pathology, 167(5), 1193-1205.

Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis. / Faulkner, Jennifer L.; Szcykalski, Lisa M.; Springer, Fredyne; Barnes, Jeffrey L.

In: American Journal of Pathology, Vol. 167, No. 5, 11.2005, p. 1193-1205.

Research output: Contribution to journalArticle

Faulkner, JL, Szcykalski, LM, Springer, F & Barnes, JL 2005, 'Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis', American Journal of Pathology, vol. 167, no. 5, pp. 1193-1205.
Faulkner, Jennifer L. ; Szcykalski, Lisa M. ; Springer, Fredyne ; Barnes, Jeffrey L. / Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis. In: American Journal of Pathology. 2005 ; Vol. 167, No. 5. pp. 1193-1205.
@article{1ec8c2790f8648618f5b07c028d82b39,
title = "Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis",
abstract = "To determine whether previous renal injury accelerates the progression, of glomeralosclerosis and interstitial fibrosis, we examined the effect of treating rats with angiotensin II after Habu venom injury. After initiating disease, we examined the origin of interstitial myofibroblasts by locating α-smooth muscle actin (α-SMA)-positive and Na+,K+-ATPase- positive cells relative to interstitial space, tubular epithelial cells, the tubular basement membrane (TBM), and vascular structures. Tubular epithelial-mesenchymal transition was also assessed by examining TBM integrity and by using Texas Red (TR)-dextran in intravital tracking experiments. The staining of α-SMA-positive myofibroblasts dramatically increased in peritubular interstitial spaces 48 hours after Habu venom plus angiotensin II, particularly in and around perivascalar and periglomerular regions, while tubular epithelial cells were α-SMA-negative. Na+,K +-ATPase-positive and TR-dextran-labeled cells were restricted to the tubular epithelium and excluded from the interstitium. By 7 and 14 days, expanded interstitial space contained only α-SMA-positive myofibroblasts without TR-dextran endocytic particles. Epithelium of atrophic tubules containing TR-dextran remained confined by surrounding interstitium and myofibroblasts. These studies indicate that early expansion of α-SMA-positive cells in the interstitium and loss of tubular area occur via encroachment of interstitial myofibroblasts from perivascular into atrophic tubular spaces rather than via epithelial-mesenchymal transition and migration of tubular cells through the TBM into the interstitium.",
author = "Faulkner, {Jennifer L.} and Szcykalski, {Lisa M.} and Fredyne Springer and Barnes, {Jeffrey L.}",
year = "2005",
month = "11",
language = "English (US)",
volume = "167",
pages = "1193--1205",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis

AU - Faulkner, Jennifer L.

AU - Szcykalski, Lisa M.

AU - Springer, Fredyne

AU - Barnes, Jeffrey L.

PY - 2005/11

Y1 - 2005/11

N2 - To determine whether previous renal injury accelerates the progression, of glomeralosclerosis and interstitial fibrosis, we examined the effect of treating rats with angiotensin II after Habu venom injury. After initiating disease, we examined the origin of interstitial myofibroblasts by locating α-smooth muscle actin (α-SMA)-positive and Na+,K+-ATPase- positive cells relative to interstitial space, tubular epithelial cells, the tubular basement membrane (TBM), and vascular structures. Tubular epithelial-mesenchymal transition was also assessed by examining TBM integrity and by using Texas Red (TR)-dextran in intravital tracking experiments. The staining of α-SMA-positive myofibroblasts dramatically increased in peritubular interstitial spaces 48 hours after Habu venom plus angiotensin II, particularly in and around perivascalar and periglomerular regions, while tubular epithelial cells were α-SMA-negative. Na+,K +-ATPase-positive and TR-dextran-labeled cells were restricted to the tubular epithelium and excluded from the interstitium. By 7 and 14 days, expanded interstitial space contained only α-SMA-positive myofibroblasts without TR-dextran endocytic particles. Epithelium of atrophic tubules containing TR-dextran remained confined by surrounding interstitium and myofibroblasts. These studies indicate that early expansion of α-SMA-positive cells in the interstitium and loss of tubular area occur via encroachment of interstitial myofibroblasts from perivascular into atrophic tubular spaces rather than via epithelial-mesenchymal transition and migration of tubular cells through the TBM into the interstitium.

AB - To determine whether previous renal injury accelerates the progression, of glomeralosclerosis and interstitial fibrosis, we examined the effect of treating rats with angiotensin II after Habu venom injury. After initiating disease, we examined the origin of interstitial myofibroblasts by locating α-smooth muscle actin (α-SMA)-positive and Na+,K+-ATPase- positive cells relative to interstitial space, tubular epithelial cells, the tubular basement membrane (TBM), and vascular structures. Tubular epithelial-mesenchymal transition was also assessed by examining TBM integrity and by using Texas Red (TR)-dextran in intravital tracking experiments. The staining of α-SMA-positive myofibroblasts dramatically increased in peritubular interstitial spaces 48 hours after Habu venom plus angiotensin II, particularly in and around perivascalar and periglomerular regions, while tubular epithelial cells were α-SMA-negative. Na+,K +-ATPase-positive and TR-dextran-labeled cells were restricted to the tubular epithelium and excluded from the interstitium. By 7 and 14 days, expanded interstitial space contained only α-SMA-positive myofibroblasts without TR-dextran endocytic particles. Epithelium of atrophic tubules containing TR-dextran remained confined by surrounding interstitium and myofibroblasts. These studies indicate that early expansion of α-SMA-positive cells in the interstitium and loss of tubular area occur via encroachment of interstitial myofibroblasts from perivascular into atrophic tubular spaces rather than via epithelial-mesenchymal transition and migration of tubular cells through the TBM into the interstitium.

UR - http://www.scopus.com/inward/record.url?scp=27544515448&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27544515448&partnerID=8YFLogxK

M3 - Article

VL - 167

SP - 1193

EP - 1205

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 5

ER -