BMP1 is not required for lung fibrosis in mice

Abstract 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 procollagen...
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Autor*in:	Hsiao-Yen Ma [verfasserIn] Elsa-Noah N’Diaye [verfasserIn] Patrick Caplazi [verfasserIn] Zhiyu Huang [verfasserIn] Alexander Arlantico [verfasserIn] Surinder Jeet [verfasserIn] Aaron Wong [verfasserIn] Hans D. Brightbill [verfasserIn] Qingling Li [verfasserIn] Weng Ruth Wong [verfasserIn] Wendy Sandoval [verfasserIn] Lucinda Tam [verfasserIn] Robert Newman [verfasserIn] Merone Roose-Girma [verfasserIn] Ning Ding [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Übergeordnetes Werk:	In: Scientific Reports - Nature Portfolio, 2011, 12(2022), 1, Seite 11
Übergeordnetes Werk:	volume:12 ; year:2022 ; number:1 ; pages:11

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41598-022-09557-3

Katalog-ID:	DOAJ07691190X

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author_variant	h y m hym e n n enn p c pc z h zh a a aa s j sj a w aw h d b hdb q l ql w r w wrw w s ws l t lt r n rn m r g mrg n d nd
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allfields	10.1038/s41598-022-09557-3 doi (DE-627)DOAJ07691190X (DE-599)DOAJe0c353ad1e8e4c3a9db3aafe0b1e52bb DE-627 ger DE-627 rakwb eng Hsiao-Yen Ma verfasserin aut BMP1 is not required for lung fibrosis in mice 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Medicine R Science Q Elsa-Noah N’Diaye verfasserin aut Patrick Caplazi verfasserin aut Zhiyu Huang verfasserin aut Alexander Arlantico verfasserin aut Surinder Jeet verfasserin aut Aaron Wong verfasserin aut Hans D. Brightbill verfasserin aut Qingling Li verfasserin aut Weng Ruth Wong verfasserin aut Wendy Sandoval verfasserin aut Lucinda Tam verfasserin aut Robert Newman verfasserin aut Merone Roose-Girma verfasserin aut Ning Ding verfasserin aut In Scientific Reports Nature Portfolio, 2011 12(2022), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:12 year:2022 number:1 pages:11 https://doi.org/10.1038/s41598-022-09557-3 kostenfrei https://doaj.org/article/e0c353ad1e8e4c3a9db3aafe0b1e52bb kostenfrei https://doi.org/10.1038/s41598-022-09557-3 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022 1 11
spelling	10.1038/s41598-022-09557-3 doi (DE-627)DOAJ07691190X (DE-599)DOAJe0c353ad1e8e4c3a9db3aafe0b1e52bb DE-627 ger DE-627 rakwb eng Hsiao-Yen Ma verfasserin aut BMP1 is not required for lung fibrosis in mice 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Medicine R Science Q Elsa-Noah N’Diaye verfasserin aut Patrick Caplazi verfasserin aut Zhiyu Huang verfasserin aut Alexander Arlantico verfasserin aut Surinder Jeet verfasserin aut Aaron Wong verfasserin aut Hans D. Brightbill verfasserin aut Qingling Li verfasserin aut Weng Ruth Wong verfasserin aut Wendy Sandoval verfasserin aut Lucinda Tam verfasserin aut Robert Newman verfasserin aut Merone Roose-Girma verfasserin aut Ning Ding verfasserin aut In Scientific Reports Nature Portfolio, 2011 12(2022), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:12 year:2022 number:1 pages:11 https://doi.org/10.1038/s41598-022-09557-3 kostenfrei https://doaj.org/article/e0c353ad1e8e4c3a9db3aafe0b1e52bb kostenfrei https://doi.org/10.1038/s41598-022-09557-3 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022 1 11
allfields_unstemmed	10.1038/s41598-022-09557-3 doi (DE-627)DOAJ07691190X (DE-599)DOAJe0c353ad1e8e4c3a9db3aafe0b1e52bb DE-627 ger DE-627 rakwb eng Hsiao-Yen Ma verfasserin aut BMP1 is not required for lung fibrosis in mice 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Medicine R Science Q Elsa-Noah N’Diaye verfasserin aut Patrick Caplazi verfasserin aut Zhiyu Huang verfasserin aut Alexander Arlantico verfasserin aut Surinder Jeet verfasserin aut Aaron Wong verfasserin aut Hans D. Brightbill verfasserin aut Qingling Li verfasserin aut Weng Ruth Wong verfasserin aut Wendy Sandoval verfasserin aut Lucinda Tam verfasserin aut Robert Newman verfasserin aut Merone Roose-Girma verfasserin aut Ning Ding verfasserin aut In Scientific Reports Nature Portfolio, 2011 12(2022), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:12 year:2022 number:1 pages:11 https://doi.org/10.1038/s41598-022-09557-3 kostenfrei https://doaj.org/article/e0c353ad1e8e4c3a9db3aafe0b1e52bb kostenfrei https://doi.org/10.1038/s41598-022-09557-3 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022 1 11
allfieldsGer	10.1038/s41598-022-09557-3 doi (DE-627)DOAJ07691190X (DE-599)DOAJe0c353ad1e8e4c3a9db3aafe0b1e52bb DE-627 ger DE-627 rakwb eng Hsiao-Yen Ma verfasserin aut BMP1 is not required for lung fibrosis in mice 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Medicine R Science Q Elsa-Noah N’Diaye verfasserin aut Patrick Caplazi verfasserin aut Zhiyu Huang verfasserin aut Alexander Arlantico verfasserin aut Surinder Jeet verfasserin aut Aaron Wong verfasserin aut Hans D. Brightbill verfasserin aut Qingling Li verfasserin aut Weng Ruth Wong verfasserin aut Wendy Sandoval verfasserin aut Lucinda Tam verfasserin aut Robert Newman verfasserin aut Merone Roose-Girma verfasserin aut Ning Ding verfasserin aut In Scientific Reports Nature Portfolio, 2011 12(2022), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:12 year:2022 number:1 pages:11 https://doi.org/10.1038/s41598-022-09557-3 kostenfrei https://doaj.org/article/e0c353ad1e8e4c3a9db3aafe0b1e52bb kostenfrei https://doi.org/10.1038/s41598-022-09557-3 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022 1 11
allfieldsSound	10.1038/s41598-022-09557-3 doi (DE-627)DOAJ07691190X (DE-599)DOAJe0c353ad1e8e4c3a9db3aafe0b1e52bb DE-627 ger DE-627 rakwb eng Hsiao-Yen Ma verfasserin aut BMP1 is not required for lung fibrosis in mice 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Medicine R Science Q Elsa-Noah N’Diaye verfasserin aut Patrick Caplazi verfasserin aut Zhiyu Huang verfasserin aut Alexander Arlantico verfasserin aut Surinder Jeet verfasserin aut Aaron Wong verfasserin aut Hans D. Brightbill verfasserin aut Qingling Li verfasserin aut Weng Ruth Wong verfasserin aut Wendy Sandoval verfasserin aut Lucinda Tam verfasserin aut Robert Newman verfasserin aut Merone Roose-Girma verfasserin aut Ning Ding verfasserin aut In Scientific Reports Nature Portfolio, 2011 12(2022), 1, Seite 11 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:12 year:2022 number:1 pages:11 https://doi.org/10.1038/s41598-022-09557-3 kostenfrei https://doaj.org/article/e0c353ad1e8e4c3a9db3aafe0b1e52bb kostenfrei https://doi.org/10.1038/s41598-022-09557-3 kostenfrei https://doaj.org/toc/2045-2322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022 1 11
language	English
source	In Scientific Reports 12(2022), 1, Seite 11 volume:12 year:2022 number:1 pages:11
sourceStr	In Scientific Reports 12(2022), 1, Seite 11 volume:12 year:2022 number:1 pages:11
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Science Q
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container_title	Scientific Reports
authorswithroles_txt_mv	Hsiao-Yen Ma @@aut@@ Elsa-Noah N’Diaye @@aut@@ Patrick Caplazi @@aut@@ Zhiyu Huang @@aut@@ Alexander Arlantico @@aut@@ Surinder Jeet @@aut@@ Aaron Wong @@aut@@ Hans D. Brightbill @@aut@@ Qingling Li @@aut@@ Weng Ruth Wong @@aut@@ Wendy Sandoval @@aut@@ Lucinda Tam @@aut@@ Robert Newman @@aut@@ Merone Roose-Girma @@aut@@ Ning Ding @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	663366712
id	DOAJ07691190X
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author	Hsiao-Yen Ma
spellingShingle	Hsiao-Yen Ma misc Medicine misc R misc Science misc Q BMP1 is not required for lung fibrosis in mice
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topic_title	BMP1 is not required for lung fibrosis in mice
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title	BMP1 is not required for lung fibrosis in mice
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title_full	BMP1 is not required for lung fibrosis in mice
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author_browse	Hsiao-Yen Ma Elsa-Noah N’Diaye Patrick Caplazi Zhiyu Huang Alexander Arlantico Surinder Jeet Aaron Wong Hans D. Brightbill Qingling Li Weng Ruth Wong Wendy Sandoval Lucinda Tam Robert Newman Merone Roose-Girma Ning Ding
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title_sort	bmp1 is not required for lung fibrosis in mice
title_auth	BMP1 is not required for lung fibrosis in mice
abstract	Abstract 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.
abstractGer	Abstract 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.
abstract_unstemmed	Abstract 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.
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title_short	BMP1 is not required for lung fibrosis in mice
url	https://doi.org/10.1038/s41598-022-09557-3 https://doaj.org/article/e0c353ad1e8e4c3a9db3aafe0b1e52bb https://doaj.org/toc/2045-2322
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