+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

The MEK/ERK signalling cascade is required for sonic hedgehog signalling pathway-mediated enhancement of proliferation and inhibition of apoptosis in normal keratinocytes



The MEK/ERK signalling cascade is required for sonic hedgehog signalling pathway-mediated enhancement of proliferation and inhibition of apoptosis in normal keratinocytes



Experimental Dermatology 23(12): 896-901



Keratinocytes (KCs) 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 KCs. Recent data suggested that the sonic hedgehog (Shh) signalling pathway plays an essential role in the proliferation and apoptosis of normal KCs. However, the mechanism remains poorly defined. Here, we provide evidence that Shh signalling induces proliferation and inhibits apoptosis in normal KCs 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 (PI3K)/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 KCs in vitro. The present study suggests that the MEK/ERK1/2 activation is part of the mechanism of Shh signal-mediated proliferation and apoptosis in normal KCs. Our results may help to elucidate the regulatory mechanisms of the Shh pathway in normal KCs and the pathogenesis of related skin disorders.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 056197489

Download citation: RISBibTeXText

PMID: 25256290

DOI: 10.1111/exd.12556


Related references

Bisphenol A stimulates adrenal cortical cell proliferation via ERβ-mediated activation of the sonic hedgehog signalling pathway. Journal of Steroid Biochemistry and Molecular Biology 178: 254-262, 2018

Recruitment of the Sonic hedgehog signalling cascade in electroconvulsive seizure-mediated regulation of adult rat hippocampal neurogenesis. European Journal of Neuroscience 22(7): 1570-1580, 2005

Bmp2 antagonizes sonic hedgehog-mediated proliferation of cerebellar granule neurones through Smad5 signalling. Development 131(13): 3159-3168, 2004

Sonic hedgehog signalling pathway regulates apoptosis through Smo protein in human umbilical vein endothelial cells. Rheumatology 54(6): 1093-1102, 2015

Sonic hedgehog signalling pathway: a complex network. Annals of Neurosciences 21(1): 28-31, 2014

The PATCHED/Sonic Hedgehog signalling pathway in superficial bladder cancer. Medecine Sciences 19(10): 920-925, 2003

Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature 412(6843): 194-198, 2001

Ectodysplasin A regulates epithelial barrier function through sonic hedgehog signalling pathway. Journal of Cellular and Molecular Medicine 22(1): 230-240, 2017

From fruitflies to mammals: mechanisms of signalling via the Sonic hedgehog pathway in lung development. Respiratory Research 1(1): 30-35, 2001

Inhibition of EGF-R/Akt signalling pathway and induction of apoptosis in human keratinocytes after treatment with light activated Curcuma longa extract. Archives of Dermatological Research 295(8-9): 329, 2004

The role of the sonic hedgehog signalling pathway in patients with midline defects and congenital hypopituitarism. Clinical Endocrinology 82(5): 728-738, 2016

The control of neuroepithelial cell adhesion by Sonic Hedgehog does not involve the PKA-dependent signalling pathway. Biology of the Cell 92(2): 166, 2000

Molecular genetic analysis of the Sonic Hedgehog/patched signalling pathway in human medulloblastomas. Proceedings of the American Association for Cancer Research Annual Meeting 42: 691, 2001

Sonic Hedgehog regulates Hes1 through a novel mechanism that is independent of canonical Notch pathway signalling. Oncogene 27(10): 1489-1500, 2007

Activation of the transcription factor Gli1 and the sonic hedgehog signalling pathway in skin tumours. Nature (London) 389(6653): 876-881, 1997