Gene Expression of Parathyroid Hormone-related Peptide of Regenerative Gastric Mucosa

再生胃粘膜甲状旁腺激素相关肽基因表达

基本信息

批准号：
09670228
负责人：
ITO Masahiro
金额：
$ 2.24万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670228/
关键词：
PTHrP PTHrP receptor gastric ulcer regenerative mucosa ets-1

项目摘要

PTHrP is the product of a gene that is expressed in many normal tissues, and the localization of PTHrP in the stomach has been demonstrated in fetal and adult animals. Gene expression of PTH/PTHrP receptor was also demonstrated in many tissues and PTHrP elicits physiological effects through PTH/PTHrP receptor in an autocrine/paracrine fashion. The purpose of this study is to elucidate the molecular mechanisms of PTHrP on mucosal regeneration and cell cycle. Acetic acid ulcer model was used in this study and the sampling tissues were processed for immunohistochemistry, in situ hybridization, and Northern blot analysis. Expression of PTHrPmRNA was decreased in the regenerative mucosa in the early phase of ulcer healing. In contrast, PTHrP receptor mRNA was overexpressed reciprocally. Expressions of EGF and TGFbeta did not involve transcription of PTHrP in an early stage of regeneration. These results suggest that PTHrP receptor expression is important in the early events of mucosal regeneration and that PTHrP involves regulation of differentiation of the regenerative epithelium in the late phase. Moreover the sense-oligo PTHrP obviously retarded ulcer healing. Overexpression of PTHrP induces PTHrP receptor down regulation and it retards the mucosal regeneration. Further studies are planned on clarification of molecular mechanism of ets-1 transcription factor of PTHrP on regeneration of the gastric mucosa.Finally, we acknowledge a support from this grant and a valuable contribution of our post doc fellows and staffs.

PTHrP 是在许多正常组织中表达的基因的产物，并且 PTHrP 在胃中的定位已在胎儿和成年动物中得到证实。 PTH/PTHrP 受体的基因表达也在许多组织中得到证实，并且 PTHrP 通过 PTH/PTHrP 受体以自分泌/旁分泌方式引发生理效应。本研究的目的是阐明PTHrP对粘膜再生和细胞周期的分子机制。本研究使用乙酸溃疡模型，并对取样组织进行免疫组织化学、原位杂交和Northern印迹分析。溃疡愈合早期再生粘膜中PTHrPmRNA表达下降。相反，PTHrP 受体 mRNA 则相反过度表达。 EGF和TGFbeta的表达在再生早期并不涉及PTHrP的转录。这些结果表明PTHrP受体表达在粘膜再生的早期事件中很重要并且PTHrP参与晚期再生上皮分化的调节。此外，正义寡PTHrP明显延缓溃疡愈合。 PTHrP 的过度表达会诱导 PTHrP 受体下调，并延缓粘膜再生。计划进一步研究阐明 PTHrP 的 ets-1 转录因子对胃粘膜再生的分子机制。最后，我们感谢这笔资助的支持以及我们的博士后研究员和工作人员的宝贵贡献。