Cargando…

BMP1 is not required for lung fibrosis in mice

Bone morphogenetic protein 1 (BMP1) belongs to the astacin/BMP1/tolloid-like family of zinc metalloproteinases, which play a fundamental role in the development and formation of extracellular matrix (ECM). BMP1 mediates the cleavage of carboxyl terminal (C-term) propeptides from procollagens, a cruc...

Descripción completa

Detalles Bibliográficos
Autores principales: Ma, Hsiao-Yen, N’Diaye, Elsa-Noah, Caplazi, Patrick, Huang, Zhiyu, Arlantico, Alexander, Jeet, Surinder, Wong, Aaron, Brightbill, Hans D., Li, Qingling, Wong, Weng Ruth, Sandoval, Wendy, Tam, Lucinda, Newman, Robert, Roose-Girma, Merone, Ding, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971496/
https://www.ncbi.nlm.nih.gov/pubmed/35361882
http://dx.doi.org/10.1038/s41598-022-09557-3
_version_ 1784679646113038336
author Ma, Hsiao-Yen
N’Diaye, Elsa-Noah
Caplazi, Patrick
Huang, Zhiyu
Arlantico, Alexander
Jeet, Surinder
Wong, Aaron
Brightbill, Hans D.
Li, Qingling
Wong, Weng Ruth
Sandoval, Wendy
Tam, Lucinda
Newman, Robert
Roose-Girma, Merone
Ding, Ning
author_facet Ma, Hsiao-Yen
N’Diaye, Elsa-Noah
Caplazi, Patrick
Huang, Zhiyu
Arlantico, Alexander
Jeet, Surinder
Wong, Aaron
Brightbill, Hans D.
Li, Qingling
Wong, Weng Ruth
Sandoval, Wendy
Tam, Lucinda
Newman, Robert
Roose-Girma, Merone
Ding, Ning
author_sort Ma, Hsiao-Yen
collection PubMed
description Bone morphogenetic protein 1 (BMP1) belongs to the astacin/BMP1/tolloid-like family of zinc metalloproteinases, which play a fundamental role in the development and formation of extracellular matrix (ECM). BMP1 mediates the cleavage of carboxyl terminal (C-term) propeptides from procollagens, a crucial step in fibrillar collagen fiber formation. Blocking BMP1 by small molecule or antibody inhibitors has been linked to anti-fibrotic activity in the preclinical models of skin, kidney and liver fibrosis. Therefore, we reason that BMP1 may be important for the pathogenesis of lung fibrosis and BMP1 could be a potential therapeutic target for progressive fibrotic disease such as idiopathic pulmonary fibrosis (IPF). Here, we observed the increased expression of BMP1 in both human IPF lungs and mouse fibrotic lungs induced by bleomycin. Furthermore, we developed an inducible Bmp1 conditional knockout (cKO) mouse strain. We found that Bmp1 deletion does not protect mice from lung fibrosis triggered by bleomycin. Moreover, we found no significant impact of BMP1 deficiency upon C-term propeptide of type I procollagen (CICP) production in the fibrotic mouse lungs. Based on these results, we propose that BMP1 is not required for lung fibrosis in mice and BMP1 may not be considered a candidate therapeutic target for IPF.
format Online
Article
Text
id pubmed-8971496
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-89714962022-04-05 BMP1 is not required for lung fibrosis in mice Ma, Hsiao-Yen N’Diaye, Elsa-Noah Caplazi, Patrick Huang, Zhiyu Arlantico, Alexander Jeet, Surinder Wong, Aaron Brightbill, Hans D. Li, Qingling Wong, Weng Ruth Sandoval, Wendy Tam, Lucinda Newman, Robert Roose-Girma, Merone Ding, Ning Sci Rep Article Bone morphogenetic protein 1 (BMP1) belongs to the astacin/BMP1/tolloid-like family of zinc metalloproteinases, which play a fundamental role in the development and formation of extracellular matrix (ECM). BMP1 mediates the cleavage of carboxyl terminal (C-term) propeptides from procollagens, a crucial step in fibrillar collagen fiber formation. Blocking BMP1 by small molecule or antibody inhibitors has been linked to anti-fibrotic activity in the preclinical models of skin, kidney and liver fibrosis. Therefore, we reason that BMP1 may be important for the pathogenesis of lung fibrosis and BMP1 could be a potential therapeutic target for progressive fibrotic disease such as idiopathic pulmonary fibrosis (IPF). Here, we observed the increased expression of BMP1 in both human IPF lungs and mouse fibrotic lungs induced by bleomycin. Furthermore, we developed an inducible Bmp1 conditional knockout (cKO) mouse strain. We found that Bmp1 deletion does not protect mice from lung fibrosis triggered by bleomycin. Moreover, we found no significant impact of BMP1 deficiency upon C-term propeptide of type I procollagen (CICP) production in the fibrotic mouse lungs. Based on these results, we propose that BMP1 is not required for lung fibrosis in mice and BMP1 may not be considered a candidate therapeutic target for IPF. Nature Publishing Group UK 2022-03-31 /pmc/articles/PMC8971496/ /pubmed/35361882 http://dx.doi.org/10.1038/s41598-022-09557-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ma, Hsiao-Yen
N’Diaye, Elsa-Noah
Caplazi, Patrick
Huang, Zhiyu
Arlantico, Alexander
Jeet, Surinder
Wong, Aaron
Brightbill, Hans D.
Li, Qingling
Wong, Weng Ruth
Sandoval, Wendy
Tam, Lucinda
Newman, Robert
Roose-Girma, Merone
Ding, Ning
BMP1 is not required for lung fibrosis in mice
title BMP1 is not required for lung fibrosis in mice
title_full BMP1 is not required for lung fibrosis in mice
title_fullStr BMP1 is not required for lung fibrosis in mice
title_full_unstemmed BMP1 is not required for lung fibrosis in mice
title_short BMP1 is not required for lung fibrosis in mice
title_sort bmp1 is not required for lung fibrosis in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971496/
https://www.ncbi.nlm.nih.gov/pubmed/35361882
http://dx.doi.org/10.1038/s41598-022-09557-3
work_keys_str_mv AT mahsiaoyen bmp1isnotrequiredforlungfibrosisinmice
AT ndiayeelsanoah bmp1isnotrequiredforlungfibrosisinmice
AT caplazipatrick bmp1isnotrequiredforlungfibrosisinmice
AT huangzhiyu bmp1isnotrequiredforlungfibrosisinmice
AT arlanticoalexander bmp1isnotrequiredforlungfibrosisinmice
AT jeetsurinder bmp1isnotrequiredforlungfibrosisinmice
AT wongaaron bmp1isnotrequiredforlungfibrosisinmice
AT brightbillhansd bmp1isnotrequiredforlungfibrosisinmice
AT liqingling bmp1isnotrequiredforlungfibrosisinmice
AT wongwengruth bmp1isnotrequiredforlungfibrosisinmice
AT sandovalwendy bmp1isnotrequiredforlungfibrosisinmice
AT tamlucinda bmp1isnotrequiredforlungfibrosisinmice
AT newmanrobert bmp1isnotrequiredforlungfibrosisinmice
AT roosegirmamerone bmp1isnotrequiredforlungfibrosisinmice
AT dingning bmp1isnotrequiredforlungfibrosisinmice