Extracellular BMP1 is the major proteinase for COOH-terminal proteolysis of type I procollagen in lung fibroblasts.

American Journal of Physiology. Cell Physiology
Elsa-Noah N'DiayeNing Ding

Abstract

Proteolytic processing of procollagens is a central step during collagen fibril formation. Bone morphogenic protein 1 (BMP1) is a metalloprotease that plays an important role in the cleavage of carboxy-terminal (COOH-terminal) propeptides from procollagens. Although the removal of propeptides is required to generate mature collagen fibrils, the contribution of BMP1 to this proteolytic process and its action site remain to be fully determined. In this study, using postnatal lung fibroblasts as a model system, we showed that genetic ablation of Bmp1 in primary murine lung fibroblasts abrogated COOH-terminal cleavage from type I procollagen as measured by COOH-terminal propeptide of type I procollagen (CICP) production. We also showed that inhibition of BMP1 by siRNA-mediated knockdown or small-molecule inhibitor reduced the vast majority of CICP production and collagen deposition in primary human lung fibroblasts. Furthermore, we discovered and characterized two antibody inhibitors for BMP1. In both postnatal lung fibroblast and organoid cultures, BMP1 blockade prevented CICP production. Together, these findings reveal a nonredundant role of extracellular BMP1 to process CICP in lung fibroblasts and suggest that development of an...Continue Reading

References

Nov 1, 1973·The Biochemical Journal·D R Eyre, M J Glimcher
May 20, 1993·Journal of Molecular Biology·P Bork, G Beckmann
Jan 19, 1996·Science·E KesslerD S Greenspan
May 14, 1996·Proceedings of the National Academy of Sciences of the United States of America·S W LiD J Prockop
May 15, 1996·The Biochemical Journal·K E KadlerJ A Chapman
May 4, 2002·Nature Reviews. Molecular Cell Biology·James J TomasekRobert A Brown
Jun 18, 2002·Journal of Structural Biology·David J S Hulmes
Mar 15, 2003·The Journal of Biological Chemistry·Mat Leighton, Karl E Kadler
May 26, 2004·The Journal of Cell Biology·Elizabeth G CantyKarl E Kadler
Mar 25, 2005·Journal of Cell Science·Elizabeth G Canty, Karl E Kadler
Apr 20, 2005·Advances in Protein Chemistry·T J Wess
Aug 16, 2006·Cellular and Molecular Life Sciences : CMLS·H A Lucero, H M Kagan
Jun 15, 2007·Matrix Biology : Journal of the International Society for Matrix Biology·Delana R HopkinsDaniel S Greenspan
Jun 27, 2007·Journal of Medicinal Chemistry·Paul V FishGavin A Whitlock
Apr 30, 2008·Methods : a Companion to Methods in Enzymology·David R EyreJiann-Jiu Wu
Apr 7, 2009·Annual Review of Biochemistry·Matthew D Shoulders, Ronald T Raines
May 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Richard BerryClair Baldock
Feb 24, 2011·Human Mutation·Katarina LindahlJoan C Marini
Mar 19, 2011·Journal of the American Society of Nephrology : JASN·Lovorka GrgurevicSlobodan Vukicevic
Dec 30, 2011·PloS One·Darren A PlumbRaymond P Boot-Handford
Apr 10, 2012·American Journal of Human Genetics·P V AsharaniThomas J Carney
Aug 15, 2012·Experimental Lung Research·Elise M MessierBeata Kosmider
Nov 9, 2012·Bioorganic & Medicinal Chemistry Letters·Eric TurtleWen-Bin Ho
Aug 8, 2013·The Journal of Clinical Investigation·Christina E BarkauskasBrigid L M Hogan
Aug 14, 2013·Proceedings of the National Academy of Sciences of the United States of America·Claudia BroderChristoph Becker-Pauly
Jan 15, 2014·Human Molecular Genetics·Alison M MuirDaniel S Greenspan
Jan 21, 2014·Advances in Experimental Medicine and Biology·Michael J Mienaltowski, David E Birk
Mar 22, 2014·American Journal of Medical Genetics. Part a·María ValenciaElsebet Ostergaard
Nov 6, 2014·Nature Reviews. Molecular Cell Biology·Janna K MouwValerie M Weaver

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Methods Mentioned

BETA
electron microscopy
PCR
biopsies
surface plasmon resonance
peptide assay
biosensor
chip
Assay
immunodepletion

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