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  • Exd 1194 f1-3

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    Svatsan Sri
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    MIF is a pro-inflammatory cytokine that is released in response to stress and LPS. It activates several signaling pathways including MAPK, PI3K/AKT, and integrin activation through various receptors such as CD74, CXCR2, CXCR4, and CD44. MIF promotes wound healing through effects on keratinocyte migration and proliferation, fibroblast migration and proliferation, macrophage migration, and wound contraction.

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    MIF is a pro-inflammatory cytokine that is released in response to stress and LPS. It activates several signaling pathways including MAPK, PI3K/AKT, and integrin activation through various receptors such as CD74, CXCR2, CXCR4, and CD44. MIF promotes wound healing through effects on keratinocyte migration and proliferation, fibroblast migration and proliferation, macrophage migration, and wound contraction.

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    4 views3 pages

    Exd 1194 f1-3

    Uploaded by

    Svatsan Sri
    MIF is a pro-inflammatory cytokine that is released in response to stress and LPS. It activates several signaling pathways including MAPK, PI3K/AKT, and integrin activation through various receptors such as CD74, CXCR2, CXCR4, and CD44. MIF promotes wound healing through effects on keratinocyte migration and proliferation, fibroblast migration and proliferation, macrophage migration, and wound contraction.

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    of 3

    Figure 1

    Pituitary Receptor
    hormone complex

    Stress response [5] CD74/CD44/CXCR


    signalling [11-13]
    Released in response
    to LPS [4] Activates MAPK
    [118, 119]

    MIF
    CSN5 signalling function Glucocorticoid
    signalling
    Inhibits CSN5 [91]
    Induces
    CSN5 controls glucocorticoid
    autocrine MIF Cytokine production
    signalling [14, 93]
    [117]
    Pro-inflammatory
    cytokine [115, 116]
    Figure 2
    MIF MIF MIF
    A
    MIF receptor

    CD44

    CXCR4 CXCR2 Gi CD74 Src-Kinase


    ?
    Ca2+
    ? PI3K/AKT MAPK/ERK
    driven by MIF receptor
    Signalling pathway

    ? Integrin PI3K/AKT p53


    ?????? Integrin
    activation
    activation MAPK/ERK
    Proliferation
    gene expression
    MMP T cell, fibroblast Migration/arrest, inflammatory Survival, apoptosis
    induction & EPC migration leukocyte recruitment inhibition
    Postulated target cell
    in wound healing

    Fibroblast
    Keratinocyte Monocyte/macrophage Fibroblast

    MIF
    B ?
    MIF
    ?

    CD74

    CXCR CD44
    Gi
    Src-Kinase

    Integrated signalling
    and/or crosstalk
    Figure 3

    (Myo)fibroblast Macrophage
    contraction migration

    A Wound
    contraction B Wound
    inflammation

    Keratinocyte Wound
    MMP-9
    migration proteolysis

    MIF Improved Impaired MIF


    Re.ep Healing Healing
    Keratinocyte Fibroblast
    proliferation proliferation

    Fibroblast Fibroblast
    migration migration

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