TY - JOUR
T1 - SRF-MRTF signaling suppresses brown adipocyte development by modulating TGF-β/BMP pathway
AU - Liu, Ruya
AU - Xiong, Xuekai
AU - Nam, Deokhwa
AU - Yechoor, Vijay
AU - Ma, Ke
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/9/15
Y1 - 2020/9/15
N2 - The SRF/MRTF and upstream signaling cascade play key roles in actin cytoskeleton organization and myocyte development. To date, how this signaling axis may function in brown adipocyte lineage commitment and maturation has not been delineated. Here we report that MRTF-SRF signaling exerts inhibitory actions on brown adipogenesis, and suppressing this negative regulation promotes brown adipocyte lineage development. During brown adipogenic differentiation, protein expressions of SRF, MRTFA/B and its transcription targets were down-regulated, and MRTFA/B shuttled from nucleus to cytoplasm. Silencing of SRF or MRTF-A/MRTF-B enhanced two distinct stages of brown adipocyte development, mesenchymal stem cell determination to brown adipocytes and terminal differentiation of brown adipogenic progenitors. We further demonstrate that the MRTF-SRF axis exerts transcriptional regulations of the TGF-β and BMP signaling pathway, critical developmental cues for brown adipocyte development. TGF-β signaling activity was significantly attenuated, whereas that of the BMP pathway augmented by inhibition of SRF or MRTF-A/MRTF-B, leading to enhanced brown adipocyte differentiation. Our study demonstrates the MRTF-SRF transcriptional cascade as a negative regulator of brown adipogenesis, through its transcriptional control of the TGF-β/BMP signaling pathways.
AB - The SRF/MRTF and upstream signaling cascade play key roles in actin cytoskeleton organization and myocyte development. To date, how this signaling axis may function in brown adipocyte lineage commitment and maturation has not been delineated. Here we report that MRTF-SRF signaling exerts inhibitory actions on brown adipogenesis, and suppressing this negative regulation promotes brown adipocyte lineage development. During brown adipogenic differentiation, protein expressions of SRF, MRTFA/B and its transcription targets were down-regulated, and MRTFA/B shuttled from nucleus to cytoplasm. Silencing of SRF or MRTF-A/MRTF-B enhanced two distinct stages of brown adipocyte development, mesenchymal stem cell determination to brown adipocytes and terminal differentiation of brown adipogenic progenitors. We further demonstrate that the MRTF-SRF axis exerts transcriptional regulations of the TGF-β and BMP signaling pathway, critical developmental cues for brown adipocyte development. TGF-β signaling activity was significantly attenuated, whereas that of the BMP pathway augmented by inhibition of SRF or MRTF-A/MRTF-B, leading to enhanced brown adipocyte differentiation. Our study demonstrates the MRTF-SRF transcriptional cascade as a negative regulator of brown adipogenesis, through its transcriptional control of the TGF-β/BMP signaling pathways.
KW - Actin cytoskeleton
KW - Brown adipogenesis
KW - Myocardin-related transcription factors
KW - Serum response factor
UR - http://www.scopus.com/inward/record.url?scp=85087294180&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087294180&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2020.110920
DO - 10.1016/j.mce.2020.110920
M3 - Article
C2 - 32603734
AN - SCOPUS:85087294180
SN - 0303-7207
VL - 515
JO - Molecular and cellular endocrinology
JF - Molecular and cellular endocrinology
M1 - 110920
ER -