Systemic inhibition of BMP1-3 decreases progression of CCl 4 -induced liver fibrosis in rats.

Autor: Grgurevic L; a Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine , University of Zagreb, Scientific Center of Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia.; b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia., Erjavec I; a Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine , University of Zagreb, Scientific Center of Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia., Grgurevic I; c Department of Gastroenterology , University Hospital Dubrava, Center for Scientific Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia., Dumic-Cule I; a Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine , University of Zagreb, Scientific Center of Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia., Brkljacic J; a Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine , University of Zagreb, Scientific Center of Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia., Verbanac D; b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia., Matijasic M; b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia., Paljetak HC; b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia., Novak R; b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia., Plecko M; a Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine , University of Zagreb, Scientific Center of Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia., Bubic-Spoljar J; b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia., Rogic D; d Department of Laboratory Diagnosis , University Hospital Centre , Zagreb , Croatia., Kufner V; a Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine , University of Zagreb, Scientific Center of Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia., Pauk M; a Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine , University of Zagreb, Scientific Center of Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia., Bordukalo-Niksic T; a Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine , University of Zagreb, Scientific Center of Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia., Vukicevic S; a Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine , University of Zagreb, Scientific Center of Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia.; c Department of Gastroenterology , University Hospital Dubrava, Center for Scientific Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia.
Jazyk: angličtina
Zdroj: Growth factors (Chur, Switzerland) [Growth Factors] 2017 Dec; Vol. 35 (6), pp. 201-215. Date of Electronic Publication: 2018 Feb 27.
DOI: 10.1080/08977194.2018.1428966
Abstrakt: Liver fibrosis is a progressive pathological process resulting in an accumulation of excess extracellular matrix proteins. We discovered that bone morphogenetic protein 1-3 (BMP1-3), an isoform of the metalloproteinase Bmp1 gene, circulates in the plasma of healthy volunteers and its neutralization decreases the progression of chronic kidney disease in 5/6 nephrectomized rats. Here, we investigated the potential role of BMP1-3 in a chronic liver disease. Rats with carbon tetrachloride (CCl 4 )-induced liver fibrosis were treated with monoclonal anti-BMP1-3 antibodies. Treatment with anti-BMP1-3 antibodies dose-dependently lowered the amount of collagen type I, downregulated the expression of Tgfb1, Itgb6, Col1a1, and Acta2 and upregulated the expression of Ctgf, Itgb1, and Dcn. Mehanistically, BMP1-3 inhibition decreased the plasma levels of transforming growth factor beta 1(TGFβ1) by prevention of its activation and lowered the prodecorin production further suppressing the TGFβ1 profibrotic effect. Our results suggest that BMP1-3 inhibitors have significant potential for decreasing the progression of fibrosis in liver cirrhosis.
Databáze: MEDLINE
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