Relaxin-2 does not Ameliorate Nephropathy in an experimental model of Type-1 Diabetes
| Autor: | Jan Rahnenführer, Franz Paul Armbruster, Thomas Dschietzig, Joerg R. Aschenbach, Jana Ruppert, Wolf-Georg Forssmann, Katharina Krause-Relle, Maud Hennequin, Hans Jürgen Grön, Ross A. D. Bathgate, Karoline von Websky, Berthold Hocher |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
lcsh:Diseases of the circulatory (Cardiovascular) system medicine.medical_specialty Diabetic nephropathy Diabetic cardiomyopathy lcsh:RC870-923 Nephropathy Mice Internal medicine Diabetes mellitus lcsh:Dermatology medicine Animals Diabetic Nephropathies Mice Knockout Inflammation Type 1 diabetes business.industry Relaxin Glomerulosclerosis General Medicine lcsh:RL1-803 lcsh:Diseases of the genitourinary system. Urology medicine.disease Streptozotocin Fibrosis Mice Inbred C57BL Disease Models Animal Diabetes Mellitus Type 1 Endocrinology lcsh:RC666-701 Nephrology Albuminuria Institut für Ernährungswissenschaft medicine.symptom Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Kidney & Blood Pressure Research, Vol 40, Iss 1, Pp 77-88 (2015) |
| Popis: | Background/Aims: 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 tubulo-interstitial 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. |
| Databáze: | OpenAIRE |
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