Abstract
Psoriasis is a chronic inflammatory skin disease with high morbidity, poor treatment methods and high rates of relapse. Keratinocyte hyperproliferation and shortened cell cycles are important pathophysiological features of psoriasis. As a known oncogene, Yes-associated protein (YAP) plays a role in promoting cell proliferation and inhibiting cell apoptosis; however, whether YAP is involved in the pathogenesis of psoriasis remains to be determined. Amphiregulin (AREG), a transcriptional target of YAP, was found to be upregulated in psoriasis, and overexpression of AREG promoted keratinocyte proliferation. In the present study, immunohistochemistry showed that YAP expression was elevated in the skin of psoriasis patients and in the Imiquimod (IMQ) mouse model of psoriasis. Knockdown of YAP in HaCaT cells inhibited cell proliferation, caused cell cycle arrest in G0/G1 phase and promoted apoptosis. These changes in YAP-knockdown HaCaT cells were related to changes in AREG expression. We concluded that YAP may play an important role in the regulation of abnormal keratinocyte proliferation via an AREG-dependent pathway and that YAP could be a new target in the treatment of psoriasis.
Highlights
Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of epidermal keratinocytes, infiltration of inflammatory cells and hyperplasia of dilated superficial dermal vessels
Because the stratum basale is the germinal zone of the epidermis, these results suggest that increased expression of Yes-associated protein (YAP) may cause hyperproliferation of keratinocytes, directly contributing to the pathogenesis of psoriasis
Keratinocyte hyperproliferation and shortened cell cycles are important pathophysiological features of psoriasis, and psoriatic keratinocytes are resistant to apoptosis
Summary
Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of epidermal keratinocytes, infiltration of inflammatory cells and hyperplasia of dilated superficial dermal vessels. Our previous studies showed that YAP was highly expressed in cutaneous SCC (cSCC), and promoted cSCC progression by regulating cell proliferation, cell cycle, apoptosis, migration and invasion[12]. We tested the hypothesis that YAP promotes the abnormal proliferation of keratinocytes through the upregulation of AREG. We examined YAP expression in the skin of psoriasis patients and in the Imiquimod (IMQ)-induced mouse model and assessed its influence on the proliferation, cell cycle and apoptosis of keratinocytes in vitro
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
