Intercellular pathways through which hypoxia stimulates fibroblast activation Hypoxia activates G proteins (Gαior Gq), which initiate PI3K/Akt-, PLC/PKC-,

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Intercellular pathways through which hypoxia stimulates fibroblast activation Hypoxia activates G proteins (Gαior Gq), which initiate PI3K/Akt-, PLC/PKC-, mTOR/p70S6K-, and ERK1/2-dependent signaling pathways that mediate hypoxic proliferative responses in ... Intercellular pathways through which hypoxia stimulates fibroblast activation Hypoxia activates G proteins (Gαior Gq), which initiate PI3K/Akt-, PLC/PKC-, mTOR/p70S6K-, and ERK1/2-dependent signaling pathways that mediate hypoxic proliferative responses in adventitial fibroblasts. PI3K stimulates Akt, which in turn contributes to the cross talk between PI3K and mTOR/p70S6K pathways. Because hypoxia induces a dramatic increase in p70S6K activity, additional signaling mechanisms are likely involved in control of the translational machinery. The cumulative effects of PI3K, Akt, mTOR, p70S6K, and ERK1/2 integrate transcriptional and translational pathways that ultimately lead to fibroblast proliferation, differentiation, and the release of mediators under hypoxic conditions. Kurt R. Stenmark et al. Physiology 2006;21:134-145 ©2006 by American Physiological Society