BMP1.3 protein as potential target in treatment of fibrosis

Abstract

: Bone morphogenetic protein 1 (BMP1) belongs to the procollagen C proteinase (PCP) family of proteases involved in development and pattern formation in various organisms. BMP1 proteinases mediate the cleavage of carboxyl peptides from procollagen molecules, which is a crucial step in fibrillar collagen synthesis. From six described alternatively spliced variants of human Bmp1 gene, only BMP1.3 protein was detected in human plasma and elevated plasma levels of this protein were found in pathological conditions such as chronic kidney disease and acute myocardial infarction. Since BMP1 is required to convert pro-collagen to collagen, its inhibition is a potential intervention for treating fibrosis. Inhibition of BMP1.3 was shown to decrease the progression of liver fibrosis in an animal model of liver cirrhosis. One of the major inflammatory signaling molecules involved in fibrogenesis in various organs is transforming growth factor beta 1 (TGF β 1), which expression is elevated in various models of induced fibrosis. Many studies have revealed that BMP1 proteases play a key role in regulation of TGF β activation. Here, we discuss BMP1.3 inhibition as a potential treatment in different pathological conditions related to the fibrosis. Testing BMP1.3 inhibition in these models indicates that the anti-BMP1.3 antibody targets relevant pathways in the development of fibrosis in different organs.