The following are the supplementary data related to

The following are the supplementary data related to this article.
Funding Sources T.I. is supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) no. 26461257, and Yokohama Foundation for Advancement of Medical Science. L.C. is supported by MEXT Government Scholarship no. 122229. These funding sources had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the paper for publication.
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Acknowledgements
Introduction Prokineticin2 (PK2), also named Bv8, is a small 8kDa protein first found in skin secretions of the frog Bombina variegate (Mollay et al., 1999). It belongs to the PK protein family, which has a conserved N-terminal sequence of AVITGA and 10 cysteines. In mammals, the PK protein family is involved in a number of biological activities such as ingestive behaviours, circadian rhythms, angiogenesis, Zebularine and inflammatory pain. Two closely related G protein-coupled receptors (PKR1 and PKR2)mediate signal transduction of PKs (Negri et al., 2004; Shojaei et al., 2008). Psoriasis, a chronic cutaneous disorder with a spectrum of clinical phenotypes including red, scaly and well-demarcated skin lesions formed by hyperproliferation of epidermal keratinocytes (KC), affects approximately 1–3% of the worldwide population (Baliwag et al., 2015; Di Meglio et al., 2014; Gottlieb, 2005; Nestle et al., 2009). Besides causing ecological burdens, psoriasis produces a severe psychosocial burden such as anxiety, depression, and perceived stress, therefore significantly impairs the quality of patients\' life (Gupta et al., 2015; Tohid et al., 2016; Villasenor-Park et al., 2012). A new emerging concept of psoriasis is that psoriasis is a chronic and disabling disease characterized by an immune-mediated inflammatory background involving skin, joints or both, often associated with several metabolic and non-metabolic comorbid diseases (Coates et al., 2016; Gupta et al., 2015; Menter, 2016). Given that psoriasis is a chronic disabling disease, the long-term safety is the major critical determinant driving the choice of treatment (Campanati et al., 2016). However, understanding of psoriasis has evolved over the years from an epidermal KC disease to an autoimmune disease to a systemic inflammatory disease (Bachelez, 2005; Nestle et al., 2009); its pathogenesis is still poorly understood. The mainstay of treatment is topical therapy, but systemic therapy is considered for the patients with moderate-to-severe disease who do not respond to topical treatments. The current available conventional systemic treatments are associated with several side effects over a long time (Asahina et al., 2016; Guerra et al., 2016). Numerous inflammatory cytokines, such as IL-17, TNF-а and IL-23, are over-produced in psoriatic skin, with their levels correlated with the severity of psoriasis disease (Baliwag et al., 2015; Kofoed et al., 2015). To target these cytokines in psoriatic disease, some anti-cytokine biologic drugs are emerging (Di Meglio et al., 2014; Eberle et al., 2016). However, as disease biomarkers, none of these cytokines has so far met the sensitivity, specificity, and accuracy criteria that would allow their translation into clinical use (Villanova et al., 2013). Psoriasis-specific pathogenesis has not been identified although inflammatory disorders play important roles in this disease as in other autoimmune diseases (Ryan et al., 2014). The cause and mechanism underlying histological symptoms in psoriasis skin remain unknown. Especially, several crucial questions for psoriasis pathogenesis remain to be elucidated including: 1) What is the initiator of psoriasis and how to initiate it? 2) Why and how do KCs abnormally proliferate and differentiate? 3) What is the mechanism triggering processing of IL-1 identified as a key player in psoriasis pathogenesis? 4) What is and how to be responsible for abnormal angiogenesis, such as dilated and contorted blood vessels in psoriatic lesions? 5) How to perpetuate inflammatory and angiogenesis disorder? Here we show that PK2, a multifunctional peptide known to promote inflammation and angiogenesis, plays a key role in psoriatic cell signaling.