{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:58:45Z","timestamp":1779379125908,"version":"3.53.1"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,4,13]],"date-time":"2019-04-13T00:00:00Z","timestamp":1555113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Limited cutaneous systemic sclerosis is one subtype of systemic sclerosis which is characterized by a prototypic multisystem fibrotic disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to further investigate the pathological mechanism of limited cutaneous systemic sclerosis (lcSSc).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The dataset GSE76807 generated from 10 lcSSc patients and five healthy controls was used. After the preprocessing of the original data, differentially expressed genes (DEGs) were identified and then performed functional analysis, protein\u2013protein interaction (PPI) network and module analysis. Additionally, the transcription factors (TFs) and miRNAs which potentially regulating DEGs were identified and the co\u2010regulatory network was constructed. Finally, DEGs targeted by current drugs were identified. Real\u2010time quantitative PCR analyses of some DEGs in mice with lcSSc were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total 203 up\u2010regulated and 189 down\u2010regulated DEGs were obtained. The up\u2010regulated genes were enriched in protein interactions at the synapses neuronal system, NCAM1 interactions, and CREB phosphorylation through the activation of CaMKII, while, cilium assembly, and endothelial form of nitric oxide synthase (eNOS) activation were enriched by down\u2010regulated genes. <jats:italic>SCRT2<\/jats:italic> and <jats:italic>RABEP1<\/jats:italic> regulated by miR\u2010218 were hub nodes in the network. <jats:italic>DRD4<\/jats:italic> and <jats:italic>GRIN2D<\/jats:italic> were the main drug targets. <jats:italic>RABEP1<\/jats:italic> and <jats:italic>SSB <\/jats:italic>were found lowly expressed in mice model with lcSSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Endothelial form of NOS activation would be suppressed, and the process of neuronal migration and outgrowth would be activated to participant in the pathological mechanism of lcSSc.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jocd.12917","type":"journal-article","created":{"date-parts":[[2019,4,13]],"date-time":"2019-04-13T10:55:46Z","timestamp":1555152946000},"page":"1938-1946","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Abnormalities in endothelial form of nitric oxide synthase is pathogenic in limited cutaneous systemic sclerosis"],"prefix":"10.1111","volume":"18","author":[{"given":"Xiu\u2010Juan","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Dermatology Renmin Hospital of Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi\u2010Ri","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Inner Mongolia People\u2019s Hospital Hohhot 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