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BACKGROUND AND PURPOSE Luminal glucose enhances intestinal Ca2+ absorption through apical Cav 1.3 channels necessary for GLUT2-mediated glucose absorption. As these reciprocal mechanisms are not well understood, we investigated the regulatory mechanisms of intestinal [Ca2+ ]cyt and SGLT1-mediated Na+ -glucose co-transports. EXPERIMENTAL APPROACH Glucose absorption and channel expression were examined in mouse upper jejunal epithelium using an Ussing chamber, immunocytochemistry and Ca2+ and Na+ imaging in single intestinal epithelial cells. KEY RESULTS Glucose induced jejunal Isc via Na+ -glucose cotransporter 1 (SGLT1) operated more efficiently in the presence of extracellular Ca2+ . A crosstalk between luminal Ca2+ entry via plasma Cav 1.3 channels and the ER Ca2+ release through ryanodine receptor (RYR) activation in small intestinal epithelial cell (IEC) or Ca2+ -induced Ca2+ release (CICR) mechanism was involve in Ca2+ -mediated jejunal glucose absorption. The ER Ca2+ release through RyR triggered basolateral Ca2+ entry or store-operated Ca2+ entry (SOCE) mechanism and the subsequent Ca2+ entry via Na+ /Ca2+ exchanger 1 (NCX1) were found to be critical in Na+ -glucose cotransporter-mediated glucose absorption. Blocking RyR, SOCE and NCX1 inhibited glucose induced [Na+ ]cyt and [Ca2+ ]cyt in single IEC and protein expression and co-localization of STIM1/Orai1, RyR1 and NCX1 were detected in IEC and jejunal mucosa. CONCLUSION AND IMPLICATIONS Luminal Ca2+ influx through Cav 1.3 triggers the CICR through RyR1 to deplete the ER Ca2+ , which induces the basolateral STIM1/Orai1-mediated SOCE mechanism and the subsequent Ca2+ entry via NCX1 to regulate intestinal glucose uptake via Ca2+ signalling. Targeting these mechanisms in IEC may help to modulate blood glucose and sodium in the metabolic disease.

Patients with cervical cancer have abnormal cell proliferation and invasion after many years of latency. However, the precise mechanisms remain unclear. Mitogen- and stress-activated kinase 2 (MSK2) is a serine/threonine kinase which displays a phenotype that promotes tumor growth and metastasis in many different types of tumors. The aim of the present study was to determine the effects of MSK2 on the proliferation of cervical cancer cells and elucidate the signaling pathways through which MSK2 exerts its effects in the pathogenesis of squamous cell carcinoma (SCC). Our results confirmed that MSK2 expression was significantly upregulated in cervical cancer cells both in vivo and in vitro. We further found that the expression patterns of paired-box gene 8 (PAX8) and MSK2 were positively correlated in cervical cancer specimens. Moreover, MSK2 knockdown inhibited the phosphorylation of PAX8 and retinoblastoma protein (RB), and suppressed the sequential expressions of cell proliferation factors E2F1 and cyclin A2, resulting in the inhibition of SCC cell proliferation and tumor formation. Thus, this study demonstrates that MSK2 has oncogenic effects in the formation and development of SCC via the PAX8/RB-E2F1/cyclin A2 axis.