title: Relaxin-2 does not ameliorate nephropathy in an experimental model of type-1 diabetes.
abstract: OBJECTIVE
  In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide – is a candidate drug for both.
  
  
  METHODS
  Low-dose (32 μg/kg/day) and high-dose (320 μg/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin.
  
  
  RESULTS
  Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-β pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis.
  
  
  CONCLUSIONS
  We investigated a model showing early DN without overt tubulointerstitial fibrosis and activation of the TGF-β-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.
authors: Thomas Bernd
authors: TB
authors: Dschietzig
authors: Katharina
authors: K
authors: Krause-Relle
authors: Maud
authors: M
authors: Hennequin
authors: Karoline
authors: K
authors: von Websky
authors: Jan
authors: J
authors: Rahnenführer
authors: Jana
authors: J
authors: Ruppert
authors: Hans Jürgen
authors: HJ
authors: Grön
authors: Franz Paul
authors: FP
authors: Armbruster
authors: Ross A D
authors: RA
authors: Bathgate
authors: Joerg R
authors: JR
authors: Aschenbach
authors: Wolf-Georg
authors: WG
authors: Forssmann
authors: Berthold
authors: B
authors: Hocher
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012065:Relaxin / Q000627:therapeutic use*
chemical_list: C095068:RLN2 protein, human; D012065:Relaxin