Induction of Sca-1 via activation of STAT3 system in the duct cells of the mouse submandibular gland by ligation of main excretory duct
Induction of Sca-1 via activation of STAT3 system in the duct cells of the mouse submandibular gland by ligation of main excretory duct
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通过结扎主排泄管激活小鼠颌下腺导管细胞中的 STAT3 系统诱导 Sca-1
DOI：
10.1152/ajpgi.00408.2010
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发表时间：
2011
影响因子：
4.5
通讯作者：
et al
中科院分区：
文献类型：
--
作者：
Purwanti N;et al
为了检查组织损伤后立即发生并与组织再生相关的最初步骤，我们采用了下颌下腺（SMG），该下颌下腺通过结扎其主要排泄管（MED）而受伤。连接小鼠SMG的MED诱导造血干细胞的蛋白标记物Sca-1的表达。在正常腺体中，Sca-1表达水平较低，主要定位于排泄管细胞。结扎后1d，几乎所有导管系统细胞的Sca-1表达均显著增加，但腺泡细胞的Sca-1表达无明显变化。Sca-1 mRNA水平在结扎后6 h开始升高，此后持续升高，直到结扎后12 h达到平台。STAT 3在其酪氨酸-705（p-STAT 3）磷酸化在结扎后立即增加，并且其定位于所有导管细胞的细胞核中。EMSA的结果揭示了核提取物与Sca-1启动子中存在的γ-干扰素激活位点（GAS）序列的特异性结合，并证实了这种结合在连接后增加。因此，本研究表明，STAT 3，已被磷酸化后MED连接，转移到细胞核，在那里它结合到GAS元件的Sca-1基因的启动子，导致促进Sca-1基因的表达。STAT 3磷酸化的实际预防降低了连接诱导的Sca-1升高。
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 ofSca-1gene, resulting in promotion ofSca-1gene expression. Actual prevention of STAT3 phosphorylation reduced the ligation-induced Sca-1 elevation.