Regulation Of Calcium Metabolism By Calcium-sensing Receptor (CASR) In Mammary Gland

Calcium as metal elements in most of the body has a variety of roles in organisms, suchas the transmission of nerve impulses, muscle contraction, the formation and development ofbone, the stability of the cytoplasmic membrane and the regulation of enzyme activity in thebody. Normal mammary gland epithelial cells and breast cancer cells express thecalcium-sensing receptor (CaSR), the master regulator of systemic calcium metabolism.PTHrP is mainly to promote the effect of calcium into the blood of the transportation in orderto maintain the blood calcium level; PMCA2’s main function is responsible for the calciumion transport within the mammary gland epithelial cells in the milk; Physiological functionsof delta FosB is involved in bone calcium deposition and bone calcium conversion; MMP-9main participation in the breast tissue and cell migration, tissue remodeling and milk somaticcell count and dairy products quality, and the relationship is very large. During lactation,activation of the CaSR in mammary epithelial cells downregulates parathyroidhormonerelated protein (PTHrP) levels in milk and in the circulation, and increases calciumtransport into milk. However, very little information is available on the role of CaSR in goatmammary gland epithelial cells (GMECs) apoptosis.In this investigation, the test results are as follows:(1)The full-length cDNA of CaSR from Xinong Saanen dairy goats was cloned, whichcontains an open-reading frame of3258bp encoding1085amino acids with a predictedmolecular weight (MW) of121.0kDa and an isoelectric point (pI) of5.65. By subcellularposition analysis found that CaSR protein mainly position in the endoplasmic reticulum(47.8%) and plasma membrane (39.1%), with the CaSR protein intracellular adjust ionconcentration, maintain normal ion steady state function of the cell. By constructingphylogenetic tree found that CaSR high homology between genes in different species,especially in mammals its homology is above90%. Among them, and the goats with thehighest homology respectively, the two species are sheep and cattle. (2)Real-time quantitative results show that the highest amount of CaSR gene expressionin heart, followed by kidney, then the breast;(3)Through CaSR agonist/inhibitor treatment, use qRT-PCR detection PTHrP severalwant to close with calcium metabolism gene expression. Results show that the CaSR expressquantity rise can promote PMCA2, delta FosB gene expression; Inhibition of PTHrP, MMP-9gene expression;(4)With CaSR agonist treatment of mammary gland epithelial cells in vitro culture, theexpression of CaSR activation, will promote the mammary gland epithelial cell apoptosis. Thedegree of apoptosis will decrease due to the expression of CaSR activity decline.This article through to the CaSR genes and Δ FosB, PMCA2, PTHrP and geneticrelationship of MMP-9, in order to further study the regulatory pathways of calcium ion inbreast lay the foundation. In production, can be used for breeding high yield lactation oflivestock, and can effectively prevent disease caused by calcium metabolism disorder ofcalcium metabolism.