Calbindin-D28k (CaBP28k) identification and regulation by 1,25-dihydroxyvitamin D3 in human choriocarcinoma cell line JEG-3

Calbindin-D28k (CaBP28k) is a cytosolic calcium (Ca2+)-binding protein expressed in tissues such as intestine, kidneys and placenta. This protein is thought to be involved in Ca2+ homeostasis. While it is well known that CaBP28k is influenced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in the intestine and kidneys, nothing is known regarding the regulation of this protein in trophoblasts of human placenta. We used JEG-3 syncytiotrophoblast-like carcinoma cell line to study the regulation of CaBP28k in correlation with 1,25(OH)2D3 receptor (VDR) following 1,25(OH)2D3 treatments. Our data demonstrated for the first time that both CaBP28k mRNA and protein were highly induced by the addition of 1,25(OH)2D3 in dose-dependent manner. Moreover, the increase and subsequent decrease in the expression of CaBP28k and VDR mRNAs indicates the transient nature of the changes in gene expression in response to 1,25(OH)2D3. This is in contrast with the temporal pattern of increasing protein for CaBP28k and VDR. We also showed that new RNA and protein syntheses are required for 1,25(OH)2D3-induced upregulation of CaBP28k. Furthermore, a 25-carboxylic ester analogue of 1,25(OH)2D3, ZK159222, used as an antagonist of 1,25(OH)2D3 signaling confirmed that indeed 1,25(OH)2D3 was implicated in the induction of CaBP28k. These novel findings are a contribution to the processes that drive CaBP28k expression regulation in human placenta.