Relaxin-1-deficient mice develop an age-related progression of renal fibrosis.
BACKGROUND
Relaxin (RLX) is a peptide hormone that stimulates the breakdown of collagen in preparation for parturition and when administered to various models of induced fibrosis. However, its significance in the aging kidney is yet to be established. In this study, we compared structural and functional changes in the kidney of aging relaxin-1 (RLX-/-) deficient mice and normal (RLX+/+) mice.


METHODS
The kidney cortex and medulla of male and female RLX+/+ and RLX-/- mice at various ages were analyzed for collagen content, concentration, and types. Histologic analysis, reverse transcription-polymerase chain reaction (RT-PCR) of relaxin and relaxin receptor mRNA expression, receptor autoradiography, glomerular isolation/analysis, and serum/urine analysis were also employed. Relaxin treatment of RLX-/- mice was used to confirm the antifibrotic effects of the peptide.


RESULTS
We demonstrate an age-related progression of renal fibrosis in male, but not female, RLX-/- mice with significantly (P < 0.05) increased tissue dry weight, collagen (type I) content and concentration. The increased collagen expression in the kidney was associated with increased glomerular matrix and to a lesser extent, interstitial fibrosis in RLX-/- mice, which also had significantly increased serum creatinine (P < 0.05) and urinary protein (P < 0.05). Treatment of RLX-/- mice with relaxin in established stages of renal fibrosis resulted in the reversal of collagen deposition.


CONCLUSIONS
This study supports the concept that relaxin may provide a means to regulate excessive collagen deposition during kidney development and in diseased states characterized by renal fibrosis.
Samuel
Chrishan S
CS
Howard Florey Institute of Experimental Physiology & Medicine, The University of Melbourne, Parkville, Victoria, Australia. c.samuel@hfi.unimelb.edu.au
Zhao
Chongxin
C
Bond
Courtney P
CP
Hewitson
Tim D
TD
Amento
Edward P
EP
Summers
Roger J
RJ
D000375:Aging / Q000235:genetics / Q000473:pathology / Q000502:physiology; D000818:Animals; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012065:Relaxin / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology
D011506:Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D011994:Recombinant Proteins; C492607:Rln1 protein, mouse; C033395:relaxin receptors; D012065:Relaxin; D003094:Collagen