Non-receptor type, proline-rich protein tyrosine kinase 2 (Pyk2) is a possible therapeutic target for Kawasaki disease.
Kawasaki disease (KD) is a paediatric vasculitis whose pathogenesis remains unclear. Based on experimental studies using a mouse model for KD, we report here that proline-rich protein tyrosine kinase 2 (Pyk2) plays a critical role in the onset of KD-like murine vasculitis. The mouse model for KD was prepared by administrating a Candida albicans water-soluble fraction (CAWS). Unlike CAWS-treated WT mice, CAWS-treated Pyk2-Knockout (Pyk2-KO) mice did not develop apparent vasculitis. A sustained increase in MIG/CXCL9 and IP-10/CXCL10, both of which have potent angiostatic activity, was observed in CAWS-treated Pyk2-KO mice. CAWS-induced activation of STAT3, which negatively regulates the expression of these chemokines, was also attenuated in macrophages derived from Pyk2-KO mice. The present study suggests that defects in Pyk2 suppress KD-like experimental vasculitis, presumably through CXCL9- and CXCL10-dependent interference with neo-angiogenesis. Since Pyk2-KO mice show no life-threatening phenotype, Pyk2 may be a promising therapeutic molecular target for KD.
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Chinatsu
C
Suzuki
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan. Electronic address: nakam993@koto.kpu-m.ac.jp.
Akihiro
A
Nakamura
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Japan.
Noriko
N
Miura
Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Kuniyoshi
K
Fukai
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Japan.
Naohito
N
Ohno
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Tomoyo
T
Yahata
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Akiko
A
Okamoto-Hamaoka
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Maiko
M
Fujii
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Ayako
A
Yoshioka
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Yuki
Y
Kuchitsu
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Kazuyuki
K
Ikeda
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan. Electronic address: khamaoka@koto.kpu-m.ac.jp.
Kenji
K
Hamaoka
D000818:Animals; D001011:Aorta / Q000378:metabolism; D002176:Candida albicans; D054357:Chemokine CXCL10 / Q000097:blood; D054370:Chemokine CXCL9 / Q000097:blood; D003331:Coronary Vessels / Q000378:metabolism; D004195:Disease Models, Animal; D051418:Focal Adhesion Kinase 2 / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism; D018345:Mice, Knockout; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism
D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D019063:Tenascin; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse
IP-10; Kawasaki disease; Pyk2; Vasculitis