title: Negative interplay of retinoic acid and TGF-β signaling mediated by TG-interacting factor to modulate mouse embryonic palate mesenchymal-cell proliferation.
abstract: Mesenchymal-cell proliferation is the main process in shelf outgrowth. Both all-trans-retinoic acid (atRA) and transforming growth factor-β3 (TGF-β3) play an important role in mouse embryonic palate mesenchymal (MEPM) cell proliferation. In the present study, we investigated the crosstalk between RA and TGF-β signaling in MEPM-cell proliferation. We found that atRA inhibited MEPM-cell proliferation by downregulating TGF-β/Smad signaling and that TGF-β3 treatment was able to antagonize RA signaling. Transforming growth-interacting factor (TGIF) is a transcriptional repressor that suppresses both TGF-β- and retinoid-driven gene transcription. Furthermore, we investigated the role of TGIF in the interaction between both TGF-β and RA signaling in MEPM-cell proliferation. The results showed that both atRA and TGF-β3 significantly increased the expression level of TGIF, and TGIF mediated the negative interaction between TGF-β and RA signaling pathways, which depended on TGIF binding to Smad2 or RARβ (RA receptor beta). Moreover, after deletion of TGIF, both the effects of atRA on TGF-β-dependent protein expression and the effects of TGF-β on RA-dependent protein expression were lost. So we conclude that there is a negative functional interplay of RA and TGF-β signaling mediated by TGIF to modulate MEPM-cell proliferation.
authors.affiliation: Public Health College, Zhengzhou University, Zhengzhou, China; Medical College, Henan University of Science & Technology, Luoyang, China.
authors.forename: Xiaozhuan
authors.initials: X
authors.lastname: Liu
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Zhang
authors.forename: Liyun
authors.initials: L
authors.lastname: Gao
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yin
authors.forename: Xinjuan
authors.initials: X
authors.lastname: Pan
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Haozhe
authors.initials: H
authors.lastname: Li
authors.forename: Zengli
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010159:Palate / Q000196:embryology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism* / Q000494:pharmacology; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; C505201:TG-interacting factor 2, mouse; D053782:Transforming Growth Factor beta3; C082925:retinoic acid receptor beta; D014212:Tretinoin
keywords: AtRA; MEPM; TGF-β3; TGIF; proliferation