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Updated: Jul 5, 2026

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
Nephrogenic systemic fibrosis is associated with transforming growth factor beta and Smad without evidence of
Brent Kelly1, Matthew Petitt, Ramon Sanchez
1Department of Dermatology, University of Texas Medical Branch, Galveston, Texas 77555-0783, USA. bckelly@utmb.edu
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.
Method:
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.
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-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.
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