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• W1993468618 abstract "Hypoxia-induced mitogenic factor (HIMF), also known as “found in inflammatory zone 1” (FIZZ1) or resistin-like molecule-α (RELMα), is a profound vasoconstrictor of the pulmonary circulation and a strong mitogenic factor in pulmonary vascular smooth muscle. To further understand the mechanism of these contractile and mitogenic responses, we examined the effect of HIMF on intracellular Ca 2+ in human pulmonary artery smooth muscle cells (SMC). Ca 2+ imaging in fluo 4-loaded human pulmonary artery SMC revealed that recombinant murine HIMF increased intracellular Ca 2+ concentration ([Ca 2+ ] i ) in a sustained and oscillatory manner. This increase occurred independent of extracellular Ca 2+ influx. Pretreatment of human pulmonary artery SMC with U-73122, a specific inhibitor of phosphatidylinositol-phospholipase C (PLC) completely prevented the HIMF-induced Ca 2+ signal. The [Ca 2+ ] i increase was also abolished by pretreatment with 2-aminoethoxydiphenyl borate (2-APB), an inositol 1,4,5-trisphosphate (IP 3 ) receptor antagonist. Ryanodine pretreatment did not affect initiation of [Ca 2+ ] i activation or internal release but reduced [Ca 2+ ] i at the plateau phase. Pretreatment with the Gα i -specific inhibitor pertussis toxin and the Gα s -specific inhibitor NF-449 did not block the Ca 2+ signal. Knockdown of Gα q/11 expression did not prevent Ca 2+ release, but the pattern of Ca 2+ release changed from the sustained oscillatory transients with prolonged plateau to a series of short [Ca 2+ ] i transients that return to baseline. However, pretreatment with the tyrosine kinase inhibitor genistein completely inhibited the internal Ca 2+ release. These results demonstrate that HIMF can stimulate intracellular Ca 2+ release in human pulmonary artery SMC through the PLC signaling pathway in an IP 3 - and tyrosine phosphorylation-dependent manner and that Gα q/11 protein-coupled receptor and ryanodine receptor contribute to the increase of [Ca 2+ ] i ." @default.
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• W1993468618 date "2009-08-01" @default.
• W1993468618 modified "2023-09-26" @default.
• W1993468618 title "Hypoxia-induced mitogenic factor/FIZZ1 induces intracellular calcium release through the PLC-IP₃ pathway" @default.
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• W1993468618 doi "https://doi.org/10.1152/ajplung.90416.2008" @default.
• W1993468618 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2742792" @default.
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