Role of FGFR2-signaling in the pathogenesis of acne

B Melnik - Dermato-endocrinology, 2009 - Taylor & Francis
B Melnik
Dermato-endocrinology, 2009Taylor & Francis
It is the purpose of this review to extend our understanding of the fibroblast growth factor
(FGF) receptor-2b-signaling network in the pathogenesis of acne. A new concept of the role
of FGFR2b-signaling in dermal-epithelial interaction for skin appendage formation,
pilosebaceous follicle homeostasis, comedogenesis, sebaceous gland proliferation and
lipogenesis is presented. The FGFR2-gain-of-function mutations in Apert syndrome and
unilateral acneiform nevus are most helpful model diseases pointing the way to androgen …
It is the purpose of this review to extend our understanding of the fibroblast growth factor (FGF) receptor-2b-signaling network in the pathogenesis of acne.  A new concept of the role of FGFR2b-signaling in dermal-epithelial interaction for skin appendage formation, pilosebaceous follicle homeostasis, comedogenesis, sebaceous gland proliferation and lipogenesis is presented. The FGFR2-gain-of-function mutations in Apert syndrome and unilateral acneiform nevus are most helpful model diseases pointing the way to androgen-dependent dermal-epithelial FGFR2-signaling in acne. Androgen-mediated up-regulation of FGFR2b-signaling in acne-prone skin appears to be involved in the pathogenesis of acne vulgaris. In organotypic skin cultures, keratinocyte-derived interleukin-1α stimulated  fibroblasts to secrete FGF7 which stimulated FGFR2b-mediated keratinocyte proliferation. Postnatal deletion of FGFR2b in mice resulted in severe sebaceous gland atrophy. The importance of FGFR2b in sebaceous gland physiology is further supported by the mode of action of anti-acne agents which have been proposed to attenuate FGFR2b-signaling. Down-regulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Down-regulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity. Insulin-like growth factor-1 (IGF-1), the mediator of growth hormone during puberty, intracts with androgen-dependent FGFR2b-signaling and links androgen- and FGF-mediated signal transduction important in sebaceous gland homeostasis. The search for a follicular defect in the dermal-epithelial regulation of growth factor-signaling in acne-prone skin appears to be a most promising approach to clarify the pathogenesis of acne.
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