PMID- 30323299
OWN - NLM
STAT- MEDLINE
DCOM- 20191104
LR  - 20211204
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Oct 15
TI  - Yes-associated protein promotes the abnormal proliferation of psoriatic 
      keratinocytes via an amphiregulin dependent pathway.
PG  - 14513
LID - 10.1038/s41598-018-32522-y [doi]
LID - 14513
AB  - 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.
FAU - Jia, Jinjing
AU  - Jia J
AUID- ORCID: 0000-0003-2297-4394
AD  - Department of Dermatology, the Second Affiliated Hospital of Guangzhou University 
      of Chinese Medicine, Guangzhou, China.
FAU - Li, Changji
AU  - Li C
AD  - Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong 
      University, School of Medicine, Xi'an, China.
FAU - Yang, Jiao
AU  - Yang J
AD  - Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong 
      University, School of Medicine, Xi'an, China.
FAU - Wang, Xin
AU  - Wang X
AD  - Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong 
      University, School of Medicine, Xi'an, China.
FAU - Li, Ruilian
AU  - Li R
AD  - Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong 
      University, School of Medicine, Xi'an, China.
FAU - Luo, Suju
AU  - Luo S
AD  - Department of Dermatology, Tianjin Medical University General Hospital, Tianjin, 
      China.
FAU - Li, Zhengxiao
AU  - Li Z
AD  - Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong 
      University, School of Medicine, Xi'an, China.
FAU - Liu, Jiankang
AU  - Liu J
AD  - Key Laboratory of Biomedical Information Engineering of the Ministry of 
      Education, School of Life Science and Technology, Xi'an Jiaotong University, 
      Xi'an, China.
AD  - Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 
      China.
FAU - Liu, Zhi
AU  - Liu Z
AD  - Department of Dermatology, University of North Carolina at Chapel Hill, Chapel 
      Hill, NC, 26599, USA.
FAU - Zheng, Yan
AU  - Zheng Y
AD  - Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong 
      University, School of Medicine, Xi'an, China. zenyan66@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181015
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (AREG protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Amphiregulin)
RN  - 0 (Phosphoproteins)
RN  - 0 (Transcription Factors)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Amphiregulin/*genetics
MH  - Animals
MH  - Apoptosis/genetics
MH  - Cell Cycle Checkpoints/genetics
MH  - Cell Line
MH  - Cell Proliferation/*genetics
MH  - Child
MH  - Female
MH  - Gene Expression Regulation/genetics
MH  - Humans
MH  - Keratinocytes/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Phosphoproteins/*genetics
MH  - Psoriasis/*genetics/pathology
MH  - Signal Transduction/genetics
MH  - Skin/metabolism/pathology
MH  - Transcription Factors
MH  - YAP-Signaling Proteins
MH  - Young Adult
PMC - PMC6189173
COIS- The authors declare no competing interests.
EDAT- 2018/10/17 06:00
MHDA- 2019/11/05 06:00
PMCR- 2018/10/15
CRDT- 2018/10/17 06:00
PHST- 2018/03/05 00:00 [received]
PHST- 2018/08/06 00:00 [accepted]
PHST- 2018/10/17 06:00 [entrez]
PHST- 2018/10/17 06:00 [pubmed]
PHST- 2019/11/05 06:00 [medline]
PHST- 2018/10/15 00:00 [pmc-release]
AID - 10.1038/s41598-018-32522-y [pii]
AID - 32522 [pii]
AID - 10.1038/s41598-018-32522-y [doi]
PST - epublish
SO  - Sci Rep. 2018 Oct 15;8(1):14513. doi: 10.1038/s41598-018-32522-y.