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

PTHrP是在许多正常组织中表达的基因的产物，并且PTHrP在胃中的定位已经在胎儿和成年动物中得到证实。PTH/PTHrP受体的基因表达在许多组织中也被证实，并且PTHrP以自分泌/旁分泌的方式通过PTH/PTHrP受体发挥生理作用。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。本研究采用乙酸溃疡模型，并对取样组织进行免疫组织化学、原位杂交和北方印迹分析。在溃疡愈合早期，再生粘膜中PTHrPmRNA表达减少。而PTHrP受体mRNA则呈高表达。EGF和TGF β的表达不涉及PTHrP在再生的早期阶段的转录。这些结果表明，PTHrP受体的表达是重要的粘膜再生的早期事件，PTHrP参与调控的再生上皮细胞的分化在晚期阶段。此外，正义寡聚PTHrP明显延缓溃疡愈合。PTHrP的过度表达可导致PTHrP受体下调，从而延缓粘膜再生。本研究计划进一步阐明PTHrP的ets-1转录因子在胃粘膜再生中的分子机制。最后，我们感谢该基金的支持以及我们的博士后研究员和工作人员的宝贵贡献。

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.