HCV core induces loss of polarity and down-regulates SHIP2 and Dlg1 expression. SHIP2 and PtdIns(3,4)P2 are localized at the basolateral membrane of polarized cells. SHIP2 siRNA and its catalytically inactive mutant disrupt epithelial polarity, and SHIP2 rescues core-induced loss of polarity through RhoA activation.
We have examined the Acylated Ghrelin (AG)/Gi pathway in different human osteoblastic cell lines. We have found that: 1) AG induces differentiation/mineralization only in mature osteoblasts; 2) the expression of GHS-R1a increases up to the mature cell stage, 3) the action is mediated via the GHS-R/Gi/cAMP pathway only in mature osteoblasts, and 4) osteoblastic cells from adolescent idiopathic scoliosis (AIS) are resistant to the AG/Gi/cAMP pathway. Altogether, these results suggested that AG uses the GHS-R1a/Gi/cAMP pathway to induce differentiation in mature osteoblasts only. This pathway is impaired in AIS osteoblasts. Understanding AG-specific pathways involved in normal and pathological osteoblasts may be useful for developing new treatments for pathologies such as AIS or osteoporosis.
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