title: Smad3 and Snail show circadian expression in human gingival fibroblasts, human mesenchymal stem cell, and in mouse liver.
abstract: Smads are intracellular signaling mediators. Complexes of Smad2 and Smad3 with Smad4 transmit transforming growth factor-beta (TGF-β) receptor-induced signaling. Snail plays important roles in mesoderm formation, gastrulation, neural crest development, and epithelial mesenchymal transition. However, it remains unknown whether Smad3 and Snail expression is circadian rhythm-dependent. Here, we showed for the first time that Smad3 and Snail show circadian expression in human gingival fibroblasts (HGF-1) and human mesenchymal stem cells (MSC) after serum shock. They also showed circadian expression in the mouse liver. We confirmed that BMAL1/2, DEC1/2, VEGF, and PER1/2/3 also show circadian expression in both HGF-1 and MSC. The mRNA peaks and phases in circadian expression of these genes differed between HGF-1 and MSC. In a luciferase assay, Smad3 promoter activity was upregulated by CLOCK/BMAL1. These findings suggest that Smad3 and Snail have circadian rhythm in vitro and vivo, and that circadian expression of Smad3 depends on CLOCK/BMAL1.
authors.affiliation: Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan. fsatoDEC1DEC2@yahoo.co.jp
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Sato
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sato
authors.forename: Daiki
authors.initials: D
authors.lastname: Jin
authors.forename: Ujjal Kumar
authors.initials: UK
authors.lastname: Bhawal
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Wu
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Noshiro
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Seino
authors.forename: Satoko
authors.initials: S
authors.lastname: Morohashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kijima
mesh_terms: D056930:ARNTL Transcription Factors / Q000096:biosynthesis; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D056926:CLOCK Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002940:Circadian Rhythm; D005347:Fibroblasts / Q000378:metabolism*; D005881:Gingiva / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D056950:Period Circadian Proteins / Q000096:biosynthesis; D051900:Smad3 Protein / Q000096:biosynthesis*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D056950:Period Circadian Proteins; D051900:Smad3 Protein; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; C422085:BHLHE41 protein, human; C403671:DELEC1 protein, human