Nephrogenic systemic fibrosis is associated with transforming growth factor beta and Smad without evidence of renin-angiotensin system involvement.
BACKGROUND
The mechanisms of fibrosis associated with nephrogenic systemic fibrosis (NSF) are largely unknown. Transforming growth factor beta (TGF-beta), a known profibrotic cytokine, is theorized to play a central role. The renin-angiotensin system has been linked with both TGF-beta expression and fibrosis in other organ systems.


OBJECTIVE
We sought to investigate whether these mechanisms were involved with NSF.


METHODS
Eleven biopsy specimens from 8 patients with NSF were evaluated by immunohistochemistry for the expression of TGF-beta, Smad 2/3, angiotensin-converting enzyme (ACE), and angiotensin II receptor 1 (AT1).


RESULTS
TGF-beta 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.


CONCLUSIONS
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-beta, 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.
Kelly
Brent
B
Department of Dermatology, University of Texas Medical Branch, Galveston, Texas 77555-0783, USA. bckelly@utmb.edu
Petitt
Matthew
M
Sanchez
Ramon
R
D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D005260:Female; D005355:Fibrosis / Q000209:etiology*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000502:physiology*; D051899:Smad2 Protein / Q000502:physiology*; D051900:Smad3 Protein / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta