Anti-Acne Agents Attenuate FGFR2 Signal Transduction in Acne

Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany.
Journal of Investigative Dermatology (Impact Factor: 7.22). 03/2009; 129(8):1868-77. DOI: 10.1038/jid.2009.8
Source: PubMed


Increased fibroblast growth factor receptor-2 (FGFR2) signaling has been proposed to be involved in acne pathogenesis and explains acne lesions in Apert syndrome and unilateral acneiform nevus associated with gain-of-function point mutations of FGFR2. If, indeed, increased FGFR2 signaling plays a major pathogenic role in follicular hyperkeratinization and sebaceous gland hypertrophy in acne, effective anti-acne drugs may attenuate increased FGFR2 signaling. The purpose of this article is to elucidate the hypothesis that known anti-acne agents may operate by downregulation of increased FGFR2 signaling. Anti-androgens suppress FGF-ligand expression, benzoyl peroxide induces FGFR2 downregulation by lysosomal receptor degradation, azelaic acid inhibits mitochondrial ATP formation required for receptor tyrosine kinase phosphorylation, tetracyclines inhibit the expression, and activity of FGFR2b downstream matrix metalloproteinases, and retinoids attenuate the FGFR2 pathway at several regulatory levels of the signal transduction cascade critical for cell cycle control, cell proliferation, differentiation, and lipogenesis. Erythromycin, a P-450 inhibitor, may interfere with FGFR2 signaling by its inhibitory effect on retinoid catabolism. The gain-of-function mutations of FGFR2 in Apert syndrome and unilateral acneiform nevus, and the proposed synergistic inhibitory interactions of anti-acne agents at various levels of the FGFR2-signaling cascade underline the role of FGFR2 signaling in the pathogenesis of acne.

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Available from: Bodo Melnik, Mar 14, 2014
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    • "FGF plays a crucial role in controlling epithelial proliferation and differentiation. At the same time androgen mediated upregulation of FGFR2b signalling is also possible which brings out follicular hyperkeratinization and sebaceous gland hypertrophy thereby [25] [26]. (6) Corticotrophin releasing hormone and urocortin bind to the CRH-receptor 1 (CRH-R1) at human sebocytes and reduces sebocyte proliferation, upregulates 3í µí»½hydroxysteroid dehydrogenase, stimulates lipogenesis and keratinocyte differentiation, and increases in local inflammation by expressing IL-6 and IL-8 [27] [28] [29]. "
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