title: Prokineticin 2 Plays a Pivotal Role in Psoriasis.
abstract: Psoriasis is histologically characterized by keratinocytes (KC) hyperproliferation, inflammation, and increased angiogenesis, but the pathological factor responsible for these symptoms is unknown. Here, a neuroendocrine peptide (prokineticin 2, PK2), is highly expressed in human and mouse psoriatic skins but no significant change in other autoimmune diseases, suggesting that PK2 is a psoriasis-specific factor. Bacterial products significantly up-regulated PK2, implying that infection induces PK2 over-expression. PK2 promoted KC and macrophage to produce interleukin-1 (IL-1), the central player of inflammation and psoriasis, which acts on adjacent fibroblast to induce inflammatory cascades and KC hyperproliferation. IL-1 feeds back on macrophages to induce PK2 production to perpetuate PK2-IL-1 positive feedback loop. PK2 also promoted angiogenesis, another psoriatic symptom. In mouse models, PK2 over-expression aggravated psoriasis while its knock-down inhibited pathological development. The results indicate that PK2 over-production perpetuates psoriatic symptoms by creating PK-2-IL-1 vicious loop. PK2 is a central player in psoriasis and a promising psoriasis-specific target.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: He
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; University of Chinese Academy of Sciences, Beijing 100009, China.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Shen
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
authors.forename: Qiumin
authors.initials: Q
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: The Department of dermatology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.affiliation: The Department of Pathology, The Affiliated Hospital of Jiangnan University Wuxi 4th People's Hospital, Wuxi 214062, Jiangsu, China.
authors.forename: Ruizhen
authors.initials: R
authors.lastname: Bai
authors.affiliation: Department of Physiology and Membrane Biology, University of California, Davis, California 95616, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Life Sciences College of Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Luan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
authors.forename: Zhiye
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. Electronic address: rongmingqiang@mail.kiz.ac.cn.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Rong
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. Electronic address: rlai@mail.kiz.ac.cn.
authors.forename: Ren
authors.initials: R
authors.lastname: Lai
mesh_terms: D000328:Adult; D000818:Animals; D001706:Biopsy; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: C410167:AIM2 protein, human; D016207:Cytokines; D004268:DNA-Binding Proteins; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C486586:Prok2 protein, mouse; D020928:Mitogen-Activated Protein Kinases
keywords: Angiogenesis; Cell proliferation; Inflammation; Interleukin-1; Prokineticin2; Psoriasis