title: Involvement of collagen-binding heat shock protein 47 and procollagen type I synthesis in idiopathic pulmonary fibrosis: contribution of type II pneumocytes to fibrosis.
abstract: The most common pathologic form of idiopathic pulmonary fibrosis is usual interstitial pneumonia, which is characterized by patchy fibrotic areas, marked increase in the number of fibroblasts and type II pneumocytes, and excessive deposition of extracellular matrix proteins, especially collagen. Heat shock protein 47 is a collagen-binding stress protein and has a specific role in intracellular processing of procollagen molecules as a collagen-specific molecular chaperone. However, its role in the causation of fibrosis in usual interstitial pneumonia is unknown. In this study, we examined the expression of heat shock protein 47 and type I procollagen in 12 patients with usual interstitial pneumonia by immunohistochemistry on sequential sections. Heat shock protein 47 was localized predominantly in alpha-smooth muscle actin-positive myofibroblasts and surfactant protein-A-positive type II pneumocytes in active fibrotic areas of usual interstitial pneumonia. Type I procollagen was also expressed in those cells. In contrast, heat shock protein 47 and type I procollagen were weakly or not at all expressed in myofibroblasts and type II pneumocytes in bronchiolitis obliterans organizing pneumonia and normal lung tissue samples obtained from excised lung cancer tissues. The numbers of heat shock protein 47- and type I procollagen-positive cells to type II pneumocytes or myofibroblasts were significantly higher in usual interstitial pneumonia than in bronchiolitis obliterans organizing pneumonia and normal lung tissue specimens. Our results suggest that myofibroblasts and type II pneumocytes play an important role in the progression of fibrosis through the induction of heat shock protein 47, which regulates the synthesis/assembly of type I procollagen in usual interstitial pneumonia. HUM PATHOL 31:1498-1505.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwashita
authors.forename: J
authors.initials: J
authors.lastname: Kadota
authors.forename: S
authors.initials: S
authors.lastname: Naito
authors.forename: H
authors.initials: H
authors.lastname: Kaida
authors.forename: Y
authors.initials: Y
authors.lastname: Ishimatsu
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Ozono
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D002452:Cell Count; D018549:Cryptogenic Organizing Pneumonia / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D019085:Fluorescent Antibody Technique, Direct; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D017563:Lung Diseases, Interstitial / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011347:Procollagen / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000199:Actins; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011347:Procollagen; C494660:SERPINH1 protein, human