The anti-fibrotic hormone relaxin is not reno-protective,despite being active,in an experimental model of type 1 diabetes

The end-point of diabetic renal disease is the accumulation of excess collagen (fibrosis/sclerosis). a number of studies have shown that the hormone relaxin (rlx) ameliorates progression of renal and non-renal fibrosis. this study assessed the anti-fibrotic potential of rlx in streptozotocin (stz)-treated transgenic mren-2 rats,an accelerated model of type 1 diabetes. eight-week old hyperglycaemic (stz-treated at week-6) and normoglycaemic (stz-untreated) animals were treated with or without recombinant human gene-2 (h2) rlx for 4-weeks (by osmotic mini-pumps) and assessed for various parameters at 12-weeks of age. hyperglycaemic mren-2 rats had elevated kidney weight/body weight ratio,glomerular filtration rate (gfr),albumin excretion rate (aer),interstitial collagen i and glomerulosclerosis (all p<0.05 vs non-diabetic controls). h2 rlx infusion had no effect on any of these parameters. increased mmp-2 levels in rlx-treated rats demonstrated that the hormone was administered and active in this model. the inability of h2 rlx to slow glomerulopathy in diabetic mren-2 rats could be in part due to the absence of its receptor,rxfp1,in rat mesangial cells,a primary mediator of diabetic glomerulosclerosis and/or the lack of any effect on tgf-β1/smad2 signalling,a well described mediator of rlx activity. these findings highlight the cell specific actions of rlx,the dissociation of anti-fibrogenic (collagen synthesis) and antifibrolytic (mmp mediated collagen degradation) properties,and the central involvement of tgf-β1 in its actions. © 2013 bentham science publishers.