PMID- 29482391 OWN - NLM STAT- MEDLINE DCOM- 20181029 LR - 20181029 IS - 1029-2292 (Electronic) IS - 0897-7194 (Linking) VI - 35 IP - 6 DP - 2017 Dec TI - Systemic inhibition of BMP1-3 decreases progression of CCl(4)-induced liver fibrosis in rats. PG - 201-215 LID - 10.1080/08977194.2018.1428966 [doi] AB - 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(TGFbeta1) by prevention of its activation and lowered the prodecorin production further suppressing the TGFbeta1 profibrotic effect. Our results suggest that BMP1-3 inhibitors have significant potential for decreasing the progression of fibrosis in liver cirrhosis. FAU - Grgurevic, Lovorka AU - Grgurevic L AD - 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. AD - b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia. FAU - Erjavec, Igor AU - Erjavec I AD - 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. FAU - Grgurevic, Ivica AU - Grgurevic I AD - c Department of Gastroenterology , University Hospital Dubrava, Center for Scientific Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia. FAU - Dumic-Cule, Ivo AU - Dumic-Cule I AD - 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. FAU - Brkljacic, Jelena AU - Brkljacic J AD - 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. FAU - Verbanac, Donatella AU - Verbanac D AD - b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia. FAU - Matijasic, Mario AU - Matijasic M AD - b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia. FAU - Paljetak, Hana Cipcic AU - Paljetak HC AD - b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia. FAU - Novak, Rudjer AU - Novak R AD - b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia. FAU - Plecko, Mihovil AU - Plecko M AD - 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. FAU - Bubic-Spoljar, Jadranka AU - Bubic-Spoljar J AD - b Center for Translational and Clinical Research, School of Medicine , University of Zagreb , Zagreb , Croatia. FAU - Rogic, Dunja AU - Rogic D AD - d Department of Laboratory Diagnosis , University Hospital Centre , Zagreb , Croatia. FAU - Kufner, Vera AU - Kufner V AD - 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. FAU - Pauk, Martina AU - Pauk M AD - 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. FAU - Bordukalo-Niksic, Tatjana AU - Bordukalo-Niksic T AD - 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. FAU - Vukicevic, Slobodan AU - Vukicevic S AD - 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. AD - c Department of Gastroenterology , University Hospital Dubrava, Center for Scientific Excellence for Reproductive and Regenerative Medicine , Zagreb , Croatia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180227 PL - England TA - Growth Factors JT - Growth factors (Chur, Switzerland) JID - 9000468 RN - 0 (Acta2 protein, rat) RN - 0 (Actins) RN - 0 (Antibodies) RN - 0 (Bone Morphogenetic Proteins) RN - 0 (Collagen Type I) RN - 0 (Dcn protein, rat) RN - 0 (Decorin) RN - 0 (Transforming Growth Factor beta) RN - CL2T97X0V0 (Carbon Tetrachloride) SB - IM MH - Actins/genetics/metabolism MH - Animals MH - Antibodies/immunology/therapeutic use MH - Bone Morphogenetic Proteins/*antagonists & inhibitors/immunology MH - Carbon Tetrachloride/toxicity MH - Cell Line MH - Collagen Type I/genetics/metabolism MH - Decorin/genetics/metabolism MH - Humans MH - Liver Cirrhosis/*drug therapy/etiology/metabolism MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Transforming Growth Factor beta/genetics/metabolism OTO - NOTNLM OT - BMP7 OT - Bone morphogenetic protein 1-3 OT - TGFbeta1 OT - integrin OT - liver fibrosis EDAT- 2018/02/28 06:00 MHDA- 2018/10/30 06:00 CRDT- 2018/02/28 06:00 PHST- 2018/02/28 06:00 [pubmed] PHST- 2018/10/30 06:00 [medline] PHST- 2018/02/28 06:00 [entrez] AID - 10.1080/08977194.2018.1428966 [doi] PST - ppublish SO - Growth Factors. 2017 Dec;35(6):201-215. doi: 10.1080/08977194.2018.1428966. Epub 2018 Feb 27.