Circulating Bone Morphogenetic Protein 1–3 Isoform Increases Renal Fibrosis

• DOI: 10.1681/asn.2010070722
• Publication Date: 2011-03-18T04:19:41Z
• Authors: Lovorka Grgurevic; Boris Macek; David R. Healy; Amy L. Brault; Igor Erjavec; Antonio Cipcic; Ivica Grgurevic; Dunja Rogic; Kresimir Galesic; Jelena Brkljacic; Ranka Stern-Padovan; Vishwas M. Paralkar; Slobodan Vukicevic
• Keywords: Follistatin

Bone morphogenetic proteins (BMPs) participate in organ regeneration through autocrine and paracrine actions, but the existence effects of these systemic circulation is unknown. Using liquid chromatography–mass spectrometry, we identified BMP6, GDF15, BMP1–3 isoform Bmp1 gene plasma samples from healthy volunteers patients with CKD. We isolated endogenous protein demonstrated that it circulates as an active enzyme, evidenced by its ability to cleave dentin matrix protein-1 vitro. In rats CKD, administration recombinant increased renal fibrosis reduced survival. contrast, a BMP1–3-neutralizing antibody fibrosis, preserved function, addition, treating neutralizing was associated low levels TGFβ1 connective tissue growth factor. HEK293 cells remnant kidneys, transcription collagen type I, TGFβ1, β-catenin, BMP7 via BMP- Wnt-independent mechanism involved signaling integrin β1 subunit. The profibrotic effect may, part, be result accompanied decrease decorin (DCN) expression. Taken together, inhibition circulating reduces suggesting this pathway may therapeutic target for