Abstract | RATIONALE:
Relaxin is a hormone that has been considered as a potential therapy for patients with fibrotic diseases. OBJECTIVES: METHODS: We analyzed gene expression data obtained from the Lung Tissue Research Consortium and correlated RXFP1 gene expression data with cross-sectional clinical and demographic data. We also employed ex vivo donor and IPF lung fibroblasts to test RXFP1 expression in vitro. We tested CGEN25009, a relaxin-like peptide, in lung fibroblasts and in bleomycin injury. MEASUREMENTS AND MAIN RESULTS: We found that RXFP1 is significantly decreased in IPF. In patients with IPF, the magnitude of RXFP1 gene expression correlated directly with diffusing capacity of the lung for carbon monoxide (P < 0.0001). Significantly less RXFP1 was detected in vitro in IPF fibroblasts than in donor controls. Transforming growth factor-β decreased RXFP1 in both donor and IPF lung fibroblasts. CGEN25009 was effective at decreasing bleomycin-induced, acid-soluble collagen deposition in vivo. The relaxin-like actions of CGEN25009 were abrogated by RXFP1 silencing in vitro, and, in comparison with donor lung fibroblasts, IPF lung fibroblasts exhibited decreased sensitivity to the relaxin-like effects of CGEN25009. CONCLUSIONS: IPF is characterized by the loss of RXFP1 expression. RXFP1 expression is directly associated with pulmonary function in patients with IPF. The relaxin-like effects of CGEN25009 in vitro are dependent on expression of RXFP1. Our data suggest that patients with IPF with the highest RXFP1 expression would be predicted to be most sensitive to relaxin-based therapies.
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Authors | Jiangning Tan, John R Tedrow, Justin A Dutta, Brenda Juan-Guardela, Mehdi Nouraie, Yanxia Chu, Humberto Trejo Bittar, Kritika Ramani, Partha S Biswas, Kristen L Veraldi, Naftali Kaminski, Yingze Zhang, Daniel J Kass |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 194
Issue 11
Pg. 1392-1402
(12 01 2016)
ISSN: 1535-4970 [Electronic] United States |
PMID | 27310652
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- RXFP1 protein, human
- Receptors, G-Protein-Coupled
- Receptors, Peptide
- Relaxin
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Topics |
- Cross-Sectional Studies
- Female
- Gene Expression
(genetics)
- Humans
- Idiopathic Pulmonary Fibrosis
(genetics, physiopathology, therapy)
- Immunoblotting
- Lung
(physiopathology)
- Male
- Microarray Analysis
- Middle Aged
- Receptors, G-Protein-Coupled
(genetics)
- Receptors, Peptide
(genetics)
- Relaxin
(therapeutic use)
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