Abstract | BACKGROUND: STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: Full-thickness skin biopsy specimens from fibrotic lesions or healthy skin were obtained from 10 patients with NSF, 16 patients with systemic sclerosis, 8 non-NSF hemodialysis patients, and 17 healthy participants. PREDICTOR: OUTCOME & MEASUREMENTS: Dermal messenger RNA and protein expression of profibrotic TGF-beta, SMAD2, SMAD3, SMAD4, SMAD7, CTGF, TIMP-1, antifibrotic SMAD7, and TNF-alpha were analyzed using real-time reverse transcription-polymerase chain reaction and immunohistologic examination on formalin-embedded tissue. RESULTS: Dermal expression of nearly all parameters differed in hemodialysis patients compared with healthy controls. In comparison to hemodialysis patients and healthy participants, we found increased messenger RNA levels for TGF-beta, the profibrotic receptor-activated SMAD2 and SMAD3, CTGF, and TIMP-1 in NSF and systemic sclerosis lesions. Few differences between NSF and non-NSF hemodialysis patients were observed for common SMAD4, inhibitory SMAD7, and TNF-alpha. LIMITATIONS: Small patient cohort. CONCLUSION: Our results suggest a profibrotic imbalance in the TGF-beta-SMAD-CTGF axis in NSF skin lesions. Significantly increased dermal expression of TGF-beta and TIMP-1 in non-NSF hemodialysis patients in comparison to healthy participants emphasizes the need for a hemodialysis control group for future investigations and suggests a pre-existing profibrotic situation in the skin of hemodialysis patients.
|
Authors | Gisela Schieren, Thilo Gambichler, Marina Skrygan, Björn Burkert, Peter Altmeyer, Lars Christian Rump, Alexander Kreuter |
Journal | American journal of kidney diseases : the official journal of the National Kidney Foundation
(Am J Kidney Dis)
Vol. 55
Issue 6
Pg. 1040-9
(Jun 2010)
ISSN: 1523-6838 [Electronic] United States |
PMID | 20430497
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- RNA, Messenger
- Smad2 Protein
- Smad3 Protein
- Tissue Inhibitor of Metalloproteinase-1
- Transforming Growth Factor beta
- Tumor Necrosis Factor-alpha
- Connective Tissue Growth Factor
|
Topics |
- Aged
- Aged, 80 and over
- Biopsy
- Cohort Studies
- Connective Tissue Growth Factor
(metabolism)
- Female
- Humans
- Kidney Diseases
(metabolism, pathology, therapy)
- Male
- Middle Aged
- Nephrogenic Fibrosing Dermopathy
(metabolism, pathology)
- RNA, Messenger
(metabolism)
- Renal Dialysis
- Scleroderma, Systemic
(metabolism, pathology)
- Signal Transduction
(physiology)
- Skin
(metabolism, pathology)
- Smad2 Protein
(metabolism)
- Smad3 Protein
(metabolism)
- Tissue Inhibitor of Metalloproteinase-1
(metabolism)
- Transforming Growth Factor beta
(metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
|