New insight into the role of MMP14 in metabolic balance
Membrane-anchored matrix metalloproteinase 14 (MMP14) is involved broadly in organ development through both its proteolytic and signal-transducing functions. Knockout of Mmp14 (KO) in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is...
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doaj-6bb34109530b4eebac8d02e398df41f02020-11-24T22:08:12ZengPeerJ Inc.PeerJ2167-83592016-07-014e214210.7717/peerj.2142New insight into the role of MMP14 in metabolic balanceHidetoshi Mori0Ramray Bhat1Alexandre Bruni-Cardoso2Emily I. Chen3Danielle M. Jorgens4Kester Coutinho5Katherine Louie6Benjamin Ben Bowen7Jamie L. Inman8Victoria Tecca9Sarah J. Lee10Sabine Becker-Weimann11Trent Northen12Motoharu Seiki13Alexander D. Borowsky14Manfred Auer15Mina J. Bissell16Department of Pathology, Center for Comparative Medicine, University of California,, Davis,, CA,, USABiological Systems and Engineering Division, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USABiological Systems and Engineering Division, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USADepartment of Pharmacology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USAMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USAMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USAEnvironmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USAEnvironmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USABiological Systems and Engineering Division, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USABiological Systems and Engineering Division, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USABiological Systems and Engineering Division, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USABiological Systems and Engineering Division, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USAEnvironmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USAInstitute of Medical, Pharmaceutical and Health Sciences, Kanazawa University,, Kanazawa,, JapanDepartment of Pathology, Center for Comparative Medicine, University of California,, Davis,, CA,, USAMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USABiological Systems and Engineering Division, Lawrence Berkeley National Laboratory,, Berkeley,, CA,, USAMembrane-anchored matrix metalloproteinase 14 (MMP14) is involved broadly in organ development through both its proteolytic and signal-transducing functions. Knockout of Mmp14 (KO) in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is poorly understood. Since the mammary gland develops after birth and is thus dependent for its functional progression on systemic and local cues, we chose it as an organ model for understanding why KO mice fail to thrive. A global analysis of the mammary glands’ proteome in the wild type (WT) and KO mice provided insight into an unexpected role of MMP14 in maintaining metabolism and homeostasis. We performed mass spectrometry and quantitative proteomics to determine the protein signatures of mammary glands from 7 to 11 days old WT and KO mice and found that KO rudiments had a significantly higher level of rate-limiting enzymes involved in catabolic pathways. Glycogen and lipid levels in KO rudiments were reduced, and the circulating levels of triglycerides and glucose were lower. Analysis of the ultrastructure of mammary glands imaged by electron microscopy revealed a significant increase in autophagy signatures in KO mice. Finally, Mmp14 silenced mammary epithelial cells displayed enhanced autophagy. Applied to a systemic level, these findings indicate that MMP14 is a crucial regulator of tissue homeostasis. If operative on a systemic level, these findings could explain how Mmp14KO litter fail to thrive due to disorder in metabolism.https://peerj.com/articles/2142.pdfAutophagyHomeostasisMammary glandGlycogenMmp14KO mouseTriglycerides |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hidetoshi Mori Ramray Bhat Alexandre Bruni-Cardoso Emily I. Chen Danielle M. Jorgens Kester Coutinho Katherine Louie Benjamin Ben Bowen Jamie L. Inman Victoria Tecca Sarah J. Lee Sabine Becker-Weimann Trent Northen Motoharu Seiki Alexander D. Borowsky Manfred Auer Mina J. Bissell |
spellingShingle |
Hidetoshi Mori Ramray Bhat Alexandre Bruni-Cardoso Emily I. Chen Danielle M. Jorgens Kester Coutinho Katherine Louie Benjamin Ben Bowen Jamie L. Inman Victoria Tecca Sarah J. Lee Sabine Becker-Weimann Trent Northen Motoharu Seiki Alexander D. Borowsky Manfred Auer Mina J. Bissell New insight into the role of MMP14 in metabolic balance PeerJ Autophagy Homeostasis Mammary gland Glycogen Mmp14KO mouse Triglycerides |
author_facet |
Hidetoshi Mori Ramray Bhat Alexandre Bruni-Cardoso Emily I. Chen Danielle M. Jorgens Kester Coutinho Katherine Louie Benjamin Ben Bowen Jamie L. Inman Victoria Tecca Sarah J. Lee Sabine Becker-Weimann Trent Northen Motoharu Seiki Alexander D. Borowsky Manfred Auer Mina J. Bissell |
author_sort |
Hidetoshi Mori |
title |
New insight into the role of MMP14 in metabolic balance |
title_short |
New insight into the role of MMP14 in metabolic balance |
title_full |
New insight into the role of MMP14 in metabolic balance |
title_fullStr |
New insight into the role of MMP14 in metabolic balance |
title_full_unstemmed |
New insight into the role of MMP14 in metabolic balance |
title_sort |
new insight into the role of mmp14 in metabolic balance |
publisher |
PeerJ Inc. |
series |
PeerJ |
issn |
2167-8359 |
publishDate |
2016-07-01 |
description |
Membrane-anchored matrix metalloproteinase 14 (MMP14) is involved broadly in organ development through both its proteolytic and signal-transducing functions. Knockout of Mmp14 (KO) in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is poorly understood. Since the mammary gland develops after birth and is thus dependent for its functional progression on systemic and local cues, we chose it as an organ model for understanding why KO mice fail to thrive. A global analysis of the mammary glands’ proteome in the wild type (WT) and KO mice provided insight into an unexpected role of MMP14 in maintaining metabolism and homeostasis. We performed mass spectrometry and quantitative proteomics to determine the protein signatures of mammary glands from 7 to 11 days old WT and KO mice and found that KO rudiments had a significantly higher level of rate-limiting enzymes involved in catabolic pathways. Glycogen and lipid levels in KO rudiments were reduced, and the circulating levels of triglycerides and glucose were lower. Analysis of the ultrastructure of mammary glands imaged by electron microscopy revealed a significant increase in autophagy signatures in KO mice. Finally, Mmp14 silenced mammary epithelial cells displayed enhanced autophagy. Applied to a systemic level, these findings indicate that MMP14 is a crucial regulator of tissue homeostasis. If operative on a systemic level, these findings could explain how Mmp14KO litter fail to thrive due to disorder in metabolism. |
topic |
Autophagy Homeostasis Mammary gland Glycogen Mmp14KO mouse Triglycerides |
url |
https://peerj.com/articles/2142.pdf |
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