CD105 maintains the thermogenic program of beige adipocytes by regulating Smad2 signaling

Ryoko Higa; Toshikatsu Hanada; Hitoshi Teranishi; Daisuke Miki; Kazuyuki Seo; Kazumasa Hada; Hiroshi Shiraishi; Hiromitsu Mimata; Reiko Hanada; Kenji Kangawa; Toshiya Murai; Kazuwa Nakao

doi:10.1016/j.mce.2018.03.008

CD105 maintains the thermogenic program of beige adipocytes by regulating Smad2 signaling

Mol Cell Endocrinol. 2018 Oct 15:474:184-193. doi: 10.1016/j.mce.2018.03.008. Epub 2018 Mar 22.

Authors

Affiliations

¹ Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
² Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan. Electronic address: thanada@oita-u.ac.jp.
³ Department of Neurophysiology, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
⁴ Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Department of Urology, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
⁵ Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
⁶ Department of Cell Biology, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
⁷ Department of Urology, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
⁸ Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; National Cerebral and Cardiovascular Center, 565-8565 Osaka, Japan.
⁹ Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Department of Psychiatry, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara, Sakyo, Kyoto 606-8507, Japan.

PMID: 29574003
DOI: 10.1016/j.mce.2018.03.008

Abstract

Beige adipocytes are thermogenic adipocytes with developmental and anatomical properties distinct from those of classical brown adipocytes. Recent studies have revealed several key molecular regulators of beige adipocyte development. CD105, also called endoglin, is a membrane protein composed of TGF-β receptor complex. It regulates TGF-β-family signal transduction and vascular formation in vivo. We report here that CD105 maintains the thermogenic gene program of beige adipocytes by regulating Smad2 signaling. Cd105^-/- adipocyte precursors showed augmented Smad2 activation and decreased expression of thermogenic genes such as Ucp1 and Prdm16-which encodes a transcriptional regulatory protein for thermogenesis-after adipogenic differentiation. Smad2 signaling augmentation by the constitutively active form of Smad2 decreased the expression of thermogenic genes in beige adipocytes. Loss of thermogenic activity in Cd105^-/- beige adipocytes was rescued by Prdm16 expression. These data reveal a novel function of CD105 in beige adipocytes: maintaining their thermogenic program by regulating Smad2 signaling.

Keywords: Beige adipocyte; CD105; Smad2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes, Beige / cytology
Adipocytes, Beige / metabolism*
Animals
Cell Differentiation / genetics
Cells, Cultured
Cytoprotection
DNA-Binding Proteins / metabolism
Endoglin / deficiency
Endoglin / metabolism*
Gene Expression Regulation
Male
Mice, Inbred C57BL
Phosphorylation
Signal Transduction*
Smad2 Protein / metabolism*
Thermogenesis* / genetics
Transcription Factors / metabolism
Uncoupling Protein 1 / genetics
Uncoupling Protein 1 / metabolism

Substances

DNA-Binding Proteins
Endoglin
Eng protein, mouse
Prdm16 protein, mouse
Smad2 Protein
Transcription Factors
Ucp1 protein, mouse
Uncoupling Protein 1