Study Of The Expression Of PTHrPin The Human Gastric Mucosa ECL Cells

Osteoporosis is a systemic skeletal disease characterized by a low bone mass and microarchitectural deterioration of bone tissue,with a consequent increased bone fragility and susceptibility to fracture.It may be affected by ages, gender,drinking,lack of estrogen or using glucocorticoid and so on.Many diseases of digestive system such as postgastrectomy,chronic liver disease and inflammatory bowel disease have a high incidence of bone rarefaction,but the mechanism remains poorly understood.Gastrectomy-evoked osteopathy has been known for over 50 years,even though many tests have revealed that the surgical removal of the whole stomach (Gastrectomy) or of the acid-producing part of the stomach(Fundectomy) results in a significant bone loss,the mechanism remains poorly understood.Neither dietary deficiency(calcium,vitamin D) nor lack of gastric acid was the main reason leading to bone loss.With the following study on the Gastrectomy-evoked bone loss,a hypothetical hormone that produced by the ECL cells(enterochromaffin-like cells,a predominant endocrine cell population in the oxyntic mucosa),referred to as gastrocalcin,has been suggested,this hormone is distinct from histamine or pancrein, but also under the control of gastrin.Gastrin has an indirect effect on bone by releasing this hormone.The increase in[Ca²⁺]in oseteolast-like cells,affected by this hormone,is mediated by an IP₃ signaling pathway.At present,we have not known this hormone perfectly in gene and protein level.A global gene expression fingerprint of the mouse stomach ECL cells was performed in 2005,researchers has found the PTHrP(parathyroid hormone-related protein,PTHrP;PTHLH) gene in the several genes that mediated by gastrin.PTHrP was first discovered as the cause of the common lethal paraneoplastic syndrome,humoral hypercalcemia of malignancy.It is now well established that PTHrP is widely expressed in many normal tissues and cell types in the body,such as the cardiovascular system,endothelial cells,smooth muscle cells and so on,it is playing important roles during both development and adulthood.As the PTHrP mRNA is unstable,and that the protein itself is liable to extensive proteolytic processing,it is a paracrine or autocrine factor,some has detected that it can influence the cell function by enter in cellular nucleus or nuclelous.Researchershave shown that PTHrP can express in smooth muscle cell in the rat gastric muscular mucosa by immunohistochemistry and molecular hybridization.It is latent smooth muscle retardation,when influenced by an external factor,such as choline or gastric distension.By the way,they also tested that PTHrP can exist in the gastric mucosa of adult rats,the expression is slender,but we have not known its effect in the normal physiology.At present,there have not any report about the expression and effect of PTHrP in the human gastric mucosal.PTHrP shares significant N-terminal amino acid sequence homology with PTH, and the two have similar structural for binding and activation of their common receptor,PTH1R(type 1 PTH receptor).They can bind to PTH1R through PKA AND PKC signal conduction PTHrP only selectively stimulate bone formation,have less adverse reaction and a fast effect,experiment and clinical research has proofed that it have no bad influence on internal environment when have a large dose medication.So it is an acceptance drugs in clinical.And if PTHrP is gastrocalcin, then we find an effective pathway to treat Gastroectomy-evoked osteopathy.As the studies on PTHrP and gastrocalcin hormone,researchers presumed that PTHrP secreted by ECL cells is the hypothetical hormone,it contributes to the regulation of calcium deposition in bone and to the maintenance of normal bone mass.The aim of this study was to obtain a basic recognition about the expression and location of PTHrP in the human normal gastric mucoal,and some possible influential factor.Objectives:To study if PTHrP can be expressed in the human gastric ECL cells,and have an initial knowledge about the relationship between PTHrP and gastrin.Material:Collect 28 specimens of normal gastric mucosa,mainly the fundus and upper body of stomach,and the same persons' blood before any treatment.Every subject had a good nutritional status or only a slight hypoproteinemia,the group was composed by 7 subject under gastroscopy and 21 specimens who under a surgery. Use RT-PCR and qPCR to test the mRNA expression of PTHrP in the gastric mucosal,and Immunohistochemistry to prove PTHrP expressed in ECL cells. ELISA and RIA were used to detect the sujects' serum PTHrP and gastrin,and then a correlation was assessed among these several index respectively.Result:RT-PCR and qRT-PCR demonstrated a faint PTHrP mRNA levels in the normal gastric mucosa,and Immunohistochemistry showed PTHrP had a weakly positive expression in ECL cells.A low level of PTHrP was tested in the plasma,it had no significant correlation with gastrin,while serum gastrin had a significant positive correlation with the relative PTHrP mRNA levels in gastric mucosa,the correlation coefficent is 0.569,P=0.002.Conclusion:PTHrP shows a low signal expression in the human gastric ECL cells, plasma PTHrP may be not an efficient way to reflect the amount that secreted by gastric mucosal.Gastrin had a significant positive correlation with the relative PTHrP mRNA levels in gastric mucosa,but we should have further study to test if gastrin can stimulate ECL cells secrete PTHrP,to know the role of PTHrP in ECL cells and if PTHrP is the hyperthetical hormone-gastroncalcin.