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
N1 - Funding Information:
The authors would like to thank D. Iracane and R. Dei-Cas for many discussions and helpful comments. Two of us (J. -F. B. and D. G.) wish to acknowledge the warm hospitality received in the Nuclear Theory Group at LLNL, where most of this work has been done. Lastly, one of us (MSW) would like to acknowledge helpful discussions with A. Sz?ke and C. Rhodes. This work has been performed under the auspices of the Department of Energy by the LLNL contract number W-7405-ENG--48.
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.
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U2 - 10.1016/j.jaad.2008.02.038
DO - 10.1016/j.jaad.2008.02.038
M3 - Article
C2 - 18485985
AN - SCOPUS:43249125755
SN - 0190-9622
VL - 58
SP - 1025
EP - 1030
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 6
ER -