title: Clinical implication of protease-activated receptor-2 in idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a lethal pulmonary disease which is characterized by progressive fibrosis. In general, the exaggerated activation of the coagulation cascade has been observed during initiation or maintenance of the fibrotic disease. In a recent study, protease-activated receptor (PAR)-2, which plays a key role in coagulation cascade, was up-regulated in IPF patients, however, its clinical implications have not been understood. The objective of the present study was to evaluate the clinical significance of PAR-2 expression in the alveolar epithelial cells of IPF patients. PAR-2 expression was evaluated by immunohistochemical method in formalin-fixed and paraffin-embedded tissues of surgical lung biopsies from patients with IPF. Fibrosis scores from hematoxylin and eosin-stained lung sections and honeycombing scores in chest CT were calculated. Medical records were retrospectively reviewed and the correlation between the expression of PAR-2 and clinical profiles were assessed. Among thirty-three IPF patients, PAR-2 expression was observed in 25 (75.8%). The lymphocyte counts in peripheral blood (2317 vs. 1753, p = 0.044) and honeycombing scores in chest CT (4.0 vs. 3.0 p = 0.046) were higher in PAR-2 positive group compared with PAR-2 negative group. During a follow-up duration of median 40.3 months, 7 (21.2%) patients died and they were all included in the PAR-2 positive group (p = 0.113). We conclude that PAR-2 is expressed in the alveolar epithelial cells of a substantial number of IPF patients, and the expression of PAR-2 significantly correlates with the extent of honeycombing shown in chest CT.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Park
authors.forename: Chang Min
authors.initials: CM
authors.lastname: Park
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Goo
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Jae-Joon
authors.initials: JJ
authors.lastname: Yim
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Kim
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Han
authors.forename: Chul-Gyu
authors.initials: CG
authors.lastname: Yoo
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044464:Receptor, PAR-2 / Q000378:metabolism*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D014797:Vital Capacity / Q000502:physiology
chemical_list: D015415:Biomarkers; D044464:Receptor, PAR-2