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    Relaxin-2 Does Not Ameliorate Nephropathy in an Experimental Model of Type-1 Diabetes (2015)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Dschietzig, Thomas Bernd
    Krause-Relle, Katharina
    Hennequin, Maud (WE 2)
    von Websky, Karoline
    Rahnenführer, Jan
    Ruppert, Jana
    Grön, Hans Jürgen
    Armbruster, Franz Paul
    Bathgate, Ross A D
    Aschenbach, Joerg R (WE 2)
    Forssmann, Wolf-Georg
    Hocher, Berthold
    Quelle
    Kidney & blood pressure research; 40(1) — S. 77–88
    ISSN: 1423-0143
    Sprache
    Englisch
    Verweise
    DOI: 10.1159/000368484
    Pubmed: 25791819
    Kontakt
    Institut für Veterinär-Physiologie

    Oertzenweg 19 b
    14163 Berlin
    +49 30 838 62600
    physiologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    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 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. © 2015 S. Karger AG, Basel.