Relaxin-2 does not ameliorate nephropathy in an experimental model of type-1 diabetes

Kidney & Blood Pressure Research
Thomas Bernd DschietzigBerthold Hocher

Abstract

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. 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. 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. We investigated a model showing early DN without overt tubulointerstitial fibrosis and ac...Continue Reading

Citations

Mar 20, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hooi Hooi NgLaura J Parry
Jun 3, 2016·British Journal of Pharmacology·C S SamuelR G Bennett
Dec 24, 2016·British Journal of Pharmacology·Elaine Unemori
Jun 18, 2017·Frontiers in Pharmacology·Benita L McVicker, Robert G Bennett
Sep 5, 2017·Frontiers in Physiology·Sandra Feijóo-BandínFrancisca Lago

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