| Background and Objectives：Gcm is expressed in Drosophila embryonic neural precursor cells, directing thedifferentiation of glial cells. However, Gcm1and Gcm2, homologs of Gcm in mammals,are specifically expressed in the placental labyrinth and the parathyroid glands, respectively.Gcm2and Foxn1gene were alternatively expressed in different areas of thethymus/parathyroid primordium in the third and fourth pharyngeal pouch in the embryonicstage, making cells differentiate whether to parathyroid or thymus. Gcm2-knockout micemiss parathyroid. Several gene variations of Gcm2were already reported in some isolatedfamilial hypoparathyroidism. In addition, Gcm2still highly expressed in matureparathyroid, suggesting its important role in maintaining adult parathyroid cell function. Ithas been confirmed that downstream genes which is regulated by Gcm2include CaSR(calcium-sensing receptor) and PTH (parathyroid hormone), which are vital to theendocrine function of parathyroid. All these studies show that Gcm2is a key molecule toparathyroid differentiation and maintenance of its endocrine function.Chronic renal failure (CRF) is a common cause of secondary hyperparathyroidism(SHPT). The calcium and phosphorus metabolism disorders caused by CRF stimulate cellproliferation of parathyroid and oversecretion of PTH, causing hyperparethyroidism.Changes of Gcm2expression are not yet clear in the process. In what form Gcm2participates in pathogenesis of SHPT, and whether it can regulates parathyroid cellproliferation or just a following reaction of proliferation needed for differentiation andmaturation remain unclear.In this study, rat model of SHPT was applied to uncover the expression changes ofGcm2by RT-PCR and Western Blot at different time point. Meanwhile, Serum intact PTHand parathyroid cell proliferations were also determined by ELISA and Ki-67immunohistochemical staining, respectively. Study of these factors in the time course ofSHPT may lay the foundation for further studies. Method：To establish rat model of secondary hyperparathyroidism,5/6nephrectomy wasperformed combined with following high phosphorus feeding. Parathyroid glands andserum were collected after4-6rats were killed at the following intervals:1, and4days, and1,2,3, and4weeks. Routine biochemical tests were performed. Changes of Serum intactPTH were detected by ELISA. The expressions of Gcm2mRNA and protein were observedby Real-time PCR and Western blot, respectively. Changes of parathyroid cell proliferationwere observed by immunohistochemistry.Results：Compared with the control group, i-PTH levels of experimental groups elevated morethan3.05folds at all time points (P <0.05); Expression of Gcm2mRNA increased by2.00,2.23,2.81,7.39(P<0.05),9.92(P<0.05) and6.82(P<0.05) folds respectively at thoseconsecutive time points, while expression of Gcm2protein slightly weakened in the firstday, and then gradually raised. But changes of parathyroid cell proliferation showed anopposite trend that it enhanced in the first week, and then returned to the normal level.Conclusion：1. The expression of Gcm2changes in the pathogenesis of secondaryhyperparathyroidism. The Gcm2mRNA increased gradually with time progress, whileprotein of Gcm2performed enhancements only after a stage of mild downregulation.2. In the pathogenesis of secondary hyperparathyroidism obvious parathyroid glandcell proliferation was observed in the first week, but it rapidly returned to the normal levelafterwards.3. In the pathogenesis of secondary hyperparathyroidism, regulation of Gcm2expression and parathyroid cell proliferation showed an opposite trend. Interaction ofparathyroid cell proliferation and changes of Gcm2expression may partly contributes to thehyperfunction of the parathyroid. |
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