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The MEK/ERK signalling cascade is required for sonic hedgehog signalling pathway‐mediated enhancement of proliferation and inhibition of apoptosis in normal keratinocytes
Author(s) -
Liu Haiyan,
Jian Qiang,
Xue Ke,
Ma Cuiling,
Xie Fang,
Wang Rui,
Liao Wenjun,
Liu Yufeng,
Chi Sumin,
Li Chengxin
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12556
Subject(s) - mapk/erk pathway , microbiology and biotechnology , hedgehog signaling pathway , signal transduction , stat protein , sonic hedgehog , kinase , cancer research , janus kinase , protein kinase b , pi3k/akt/mtor pathway , biology , chemistry , stat3
Keratinocytes ( KC s) play a critical role in maintaining the cutaneous structure and are involved in various physiological and pathologic processes of the skin. Many inflammatory skin diseases and skin cancers result from excessive proliferation and insufficient apoptosis of KC s. Recent data suggested that the sonic hedgehog (Shh) signalling pathway plays an essential role in the proliferation and apoptosis of normal KC s. However, the mechanism remains poorly defined. Here, we provide evidence that Shh signalling induces proliferation and inhibits apoptosis in normal KC s via cyclin D1 and Bcl2 in an extracellular signal‐regulatedkinase ( MEK )/extracellular signal‐regulated kinase ( ERK )‐dependent manner. In addition, the effect is independent of phosphoinositide‐3 kinase ( PI 3K)/ AKT or Janus kinase/signal transducer and activator of transcription ( JAK / STAT ) 1/3 pathways. Furthermore, we observed that epidermal growth factor receptor ( EGFR ) signalling modulates the activity of Shh signalling pathway; besides, Shh and EGFR signalling act additively to induce the ERK activation and the increases in cyclin D1 and Bcl2 thereby affecting proliferation and apoptosis in KC s in vitro . The present study suggests that the MEK / ERK 1/2 activation is part of the mechanism of Shh signal‐mediated proliferation and apoptosis in normal KC s. Our results may help to elucidate the regulatory mechanisms of the Shh pathway in normal KC s and the pathogenesis of related skin disorders.