Nephrogenic systemic fibrosis is associated with transforming growth factor β and Smad without evidence of renin-angiotensin system involvement

Brent Kelly, Matthew Petitt, Ramon Sanchez

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: The mechanisms of fibrosis associated with nephrogenic systemic fibrosis (NSF) are largely unknown. Transforming growth factor beta (TGF-β), a known profibrotic cytokine, is theorized to play a central role. The renin-angiotensin system has been linked with both TGF-β expression and fibrosis in other organ systems. Objective: We sought to investigate whether these mechanisms were involved with NSF. Method: Eleven biopsy specimens from 8 patients with NSF were evaluated by immunohistochemistry for the expression of TGF-β, Smad 2/3, angiotensin-converting enzyme (ACE), and angiotensin II receptor 1 (AT1). Results: TGF-β was detected in 8 of 11 samples of NSF. Smad 2/3 nuclear staining was seen in 8 of 11 samples. Conversely, only faint staining for ACE was seen in 2 of the 11 specimens. No AT1 staining was seen. Limitations: We did not perform our studies on a cohort of comparable patients with renal dysfunction without NSF. Our technique may not have been sufficiently sensitive to detect renin-angiotensin system involvement. Conclusions: TGF-β, as well as its second messengers, Smad 2/3, appears to be associated with the fibrosis seen in NSF. No definitive evidence of renin-angiotensin system involvement could be determined.

Original languageEnglish (US)
Pages (from-to)1025-1030
Number of pages6
JournalJournal of the American Academy of Dermatology
Volume58
Issue number6
DOIs
StatePublished - Jun 2008

Fingerprint

Nephrogenic Fibrosing Dermopathy
Transforming Growth Factors
Renin-Angiotensin System
Transforming Growth Factor beta
Fibrosis
Staining and Labeling
Angiotensin Receptors
Second Messenger Systems
Peptidyl-Dipeptidase A
Immunohistochemistry
Cytokines
Kidney
Biopsy

ASJC Scopus subject areas

  • Dermatology

Cite this

@article{8e470861c32d47068a647d5a0390b3fa,
title = "Nephrogenic systemic fibrosis is associated with transforming growth factor β and Smad without evidence of renin-angiotensin system involvement",
abstract = "Background: The mechanisms of fibrosis associated with nephrogenic systemic fibrosis (NSF) are largely unknown. Transforming growth factor beta (TGF-β), a known profibrotic cytokine, is theorized to play a central role. The renin-angiotensin system has been linked with both TGF-β expression and fibrosis in other organ systems. Objective: We sought to investigate whether these mechanisms were involved with NSF. Method: Eleven biopsy specimens from 8 patients with NSF were evaluated by immunohistochemistry for the expression of TGF-β, Smad 2/3, angiotensin-converting enzyme (ACE), and angiotensin II receptor 1 (AT1). Results: TGF-β was detected in 8 of 11 samples of NSF. Smad 2/3 nuclear staining was seen in 8 of 11 samples. Conversely, only faint staining for ACE was seen in 2 of the 11 specimens. No AT1 staining was seen. Limitations: We did not perform our studies on a cohort of comparable patients with renal dysfunction without NSF. Our technique may not have been sufficiently sensitive to detect renin-angiotensin system involvement. Conclusions: TGF-β, as well as its second messengers, Smad 2/3, appears to be associated with the fibrosis seen in NSF. No definitive evidence of renin-angiotensin system involvement could be determined.",
author = "Brent Kelly and Matthew Petitt and Ramon Sanchez",
year = "2008",
month = "6",
doi = "10.1016/j.jaad.2008.02.038",
language = "English (US)",
volume = "58",
pages = "1025--1030",
journal = "Journal of the American Academy of Dermatology",
issn = "0190-9622",
publisher = "Mosby Inc.",
number = "6",

}

TY - JOUR

T1 - Nephrogenic systemic fibrosis is associated with transforming growth factor β and Smad without evidence of renin-angiotensin system involvement

AU - Kelly, Brent

AU - Petitt, Matthew

AU - Sanchez, Ramon

PY - 2008/6

Y1 - 2008/6

N2 - Background: The mechanisms of fibrosis associated with nephrogenic systemic fibrosis (NSF) are largely unknown. Transforming growth factor beta (TGF-β), a known profibrotic cytokine, is theorized to play a central role. The renin-angiotensin system has been linked with both TGF-β expression and fibrosis in other organ systems. Objective: We sought to investigate whether these mechanisms were involved with NSF. Method: Eleven biopsy specimens from 8 patients with NSF were evaluated by immunohistochemistry for the expression of TGF-β, Smad 2/3, angiotensin-converting enzyme (ACE), and angiotensin II receptor 1 (AT1). Results: TGF-β was detected in 8 of 11 samples of NSF. Smad 2/3 nuclear staining was seen in 8 of 11 samples. Conversely, only faint staining for ACE was seen in 2 of the 11 specimens. No AT1 staining was seen. Limitations: We did not perform our studies on a cohort of comparable patients with renal dysfunction without NSF. Our technique may not have been sufficiently sensitive to detect renin-angiotensin system involvement. Conclusions: TGF-β, as well as its second messengers, Smad 2/3, appears to be associated with the fibrosis seen in NSF. No definitive evidence of renin-angiotensin system involvement could be determined.

AB - Background: The mechanisms of fibrosis associated with nephrogenic systemic fibrosis (NSF) are largely unknown. Transforming growth factor beta (TGF-β), a known profibrotic cytokine, is theorized to play a central role. The renin-angiotensin system has been linked with both TGF-β expression and fibrosis in other organ systems. Objective: We sought to investigate whether these mechanisms were involved with NSF. Method: Eleven biopsy specimens from 8 patients with NSF were evaluated by immunohistochemistry for the expression of TGF-β, Smad 2/3, angiotensin-converting enzyme (ACE), and angiotensin II receptor 1 (AT1). Results: TGF-β was detected in 8 of 11 samples of NSF. Smad 2/3 nuclear staining was seen in 8 of 11 samples. Conversely, only faint staining for ACE was seen in 2 of the 11 specimens. No AT1 staining was seen. Limitations: We did not perform our studies on a cohort of comparable patients with renal dysfunction without NSF. Our technique may not have been sufficiently sensitive to detect renin-angiotensin system involvement. Conclusions: TGF-β, as well as its second messengers, Smad 2/3, appears to be associated with the fibrosis seen in NSF. No definitive evidence of renin-angiotensin system involvement could be determined.

UR - http://www.scopus.com/inward/record.url?scp=43249125755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43249125755&partnerID=8YFLogxK

U2 - 10.1016/j.jaad.2008.02.038

DO - 10.1016/j.jaad.2008.02.038

M3 - Article

C2 - 18485985

AN - SCOPUS:43249125755

VL - 58

SP - 1025

EP - 1030

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

SN - 0190-9622

IS - 6

ER -