New insight into the role of MMP14 in metabolic balance

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere2142
JournalPeerJ
Volume2016
Issue number7
DOIs
StatePublished - 2016

Fingerprint

Matrix Metalloproteinase 14
metalloproteinases
Human Mammary Glands
mammary glands
Metabolism
Tissue homeostasis
mice
autophagy
Autophagy
Proteome
homeostasis
Glycogen
Homeostasis
Electron microscopy
Mass spectrometry
Triglycerides
Premature Mortality
metabolism
Membranes
Lipids

Keywords

  • Autophagy
  • Energy metabolism
  • Glucose
  • Glycogen
  • Homeostasis
  • Lipids
  • Mammary gland
  • Matrix metalloproteinase 14
  • Mmp14KO mouse
  • Triglycerides

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Mori, H., Bhat, R., Bruni-Cardoso, A., Chen, E. I., Jorgens, D. M., Coutinho, K., ... Bissell, M. J. (2016). New insight into the role of MMP14 in metabolic balance. PeerJ, 2016(7), [e2142]. https://doi.org/10.7717/peerj.2142

New insight into the role of MMP14 in metabolic balance. / Mori, Hidetoshi; Bhat, Ramray; Bruni-Cardoso, Alexandre; Chen, Emily I.; Jorgens, Danielle M.; Coutinho, Kester; Louie, Katherine; Bowen, Benjamin Ben; Inman, Jamie L.; Tecca, Victoria; Lee, Sarah J.; Becker-Weimann, Sabine; Northen, Trent; Seiki, Motoharu; Borowsky, Alexander D; Auer, Manfred; Bissell, Mina J.

In: PeerJ, Vol. 2016, No. 7, e2142, 2016.

Research output: Contribution to journalArticle

Mori, H, Bhat, R, Bruni-Cardoso, A, Chen, EI, Jorgens, DM, Coutinho, K, Louie, K, Bowen, BB, Inman, JL, Tecca, V, Lee, SJ, Becker-Weimann, S, Northen, T, Seiki, M, Borowsky, AD, Auer, M & Bissell, MJ 2016, 'New insight into the role of MMP14 in metabolic balance', PeerJ, vol. 2016, no. 7, e2142. https://doi.org/10.7717/peerj.2142
Mori H, Bhat R, Bruni-Cardoso A, Chen EI, Jorgens DM, Coutinho K et al. New insight into the role of MMP14 in metabolic balance. PeerJ. 2016;2016(7). e2142. https://doi.org/10.7717/peerj.2142
Mori, Hidetoshi ; Bhat, Ramray ; Bruni-Cardoso, Alexandre ; Chen, Emily I. ; Jorgens, Danielle M. ; Coutinho, Kester ; Louie, Katherine ; Bowen, Benjamin Ben ; Inman, Jamie L. ; Tecca, Victoria ; Lee, Sarah J. ; Becker-Weimann, Sabine ; Northen, Trent ; Seiki, Motoharu ; Borowsky, Alexander D ; Auer, Manfred ; Bissell, Mina J. / New insight into the role of MMP14 in metabolic balance. In: PeerJ. 2016 ; Vol. 2016, No. 7.
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