title: Induction of Sca-1 via activation of STAT3 system in the duct cells of the mouse submandibular gland by ligation of the main excretory duct.
abstract: To examine the very initial step that takes place immediately after tissue injury and is linked to tissue regeneration, we employed the submandibular gland (SMG), which was injured by ligation of its main excretory duct (MED). Ligation of the MED of the SMG in mice induced the expression of Sca-1, a protein marker of hematopoietic stem cells. In the normal gland, a low level of Sca-1 was expressed, which was localized predominantly in the excretory duct cells. At 1 day after ligation, Sca-1 expression increased prominently in almost all of cells in the duct system, but not in the acinar cells. The level of Sca-1 mRNA had begun to increase at 6 h after ligation and continuously rose thereafter until it reached a plateau, which occurred ∼12 h after ligation. STAT3 phosphorylated at its tyrosine-705 (p-STAT3) in the ligated gland increased immediately after ligation, and it was localized in the nuclei of all duct cells. The results of an EMSA revealed the specific binding of a nuclear extract to the sequence of the γ-interferon activation site (GAS) present in the Sca-1 promoter and confirmed that such binding increased after ligation. Thus the present study suggests that STAT3, having been phosphorylated following MED ligation, was transferred to the nucleus, where it bound to the GAS element in the promoter of Sca-1 gene, resulting in promotion of Sca-1 gene expression. Actual prevention of STAT3 phosphorylation reduced the ligation-induced Sca-1 elevation.
authors.affiliation: Department of Molecular Oral Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho, Tokushima-shi, Japan.
authors.forename: Nunuk
authors.initials: N
authors.lastname: Purwanti
authors.forename: Mileva Ratko
authors.initials: MR
authors.lastname: Karabasil
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Matsuo
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Purevjav
authors.initials: P
authors.lastname: Javkhlan
authors.forename: Ahmad
authors.initials: A
authors.lastname: Azlina
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Chenjuan
authors.initials: C
authors.lastname: Yao
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Akamatsu
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hosoi
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D008026:Ligation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018987:Salivary Ducts / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D013363:Submandibular Gland / Q000166:cytology / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D050796:STAT3 Transcription Factor