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Relaxin down-regulates renal fibroblast function and promotes matrix remodelling in vitro
Rosemary Masterson1, Tim D Hewitson, Kristen Kelynack
1Department of Nephrology, Royal Melbourne Hospital, and Department of Medicine, University of Melbourne, Victoria, Australia. Rosemary.Masterson@mh.org.au
Summary
Relaxin significantly reduces renal fibroblast activity and collagen production, offering potential as an antifibrotic therapy for kidney disease. This study shows relaxin down-regulates fibroblast function and promotes matrix remodeling.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Renal fibroblasts are key players in tubulointerstitial fibrosis.
- Antifibrotic strategies aim to down-regulate these cells.
- The polypeptide hormone relaxin shows promise as an antifibrotic agent.
Purpose of the Study:
- To investigate the antifibrotic mechanisms of relaxin on renal fibroblasts in vitro.
- To elucidate how relaxin affects fibroblast activity, collagen synthesis, and matrix remodeling.
Main Methods:
- Rat cortical fibroblasts were cultured from kidneys post-unilateral ureteric obstruction.
- Relaxin radio-receptor assay determined relaxin binding to fibroblasts.
- Functional studies assessed effects of H2 relaxin on fibroblast kinetics, alpha-smooth muscle actin (alpha-SMA) expression, collagen synthesis, collagenase production, and collagen-I lattice contraction.
- CTGF mRNA expression was measured via northern analysis.
Main Results:
- H2 relaxin bound to renal fibroblasts, with low receptor numbers.
- Transforming growth factor-beta 1 (TGF-beta 1)-induced fibroblast proliferation was abrogated by H2 relaxin.
- H2 relaxin decreased alpha-SMA expression and collagen synthesis, while increasing collagenase production.
- TGF-beta 1-stimulated collagen-I lattice contraction was inhibited by H2 relaxin.
- No significant effect of H2 relaxin on CTGF mRNA expression was observed.
Conclusions:
- Relaxin's antifibrotic effects stem from down-regulating fibroblast activity, increasing collagenase synthesis, and remodeling collagen-I lattices.
- An interaction between TGF-beta 1 and H2 relaxin exists, but not via CTGF mRNA reduction.