title: The definition of fibrogenic processes in fibroblastic foci of idiopathic pulmonary fibrosis based on morphometric quantification of extracellular matrices.
abstract: There is limited information regarding the process of tissue remodeling in fibroblastic foci associated with idiopathic pulmonary fibrosis. The aim of this study was to identify the different pathologic stages of tissue remodeling in fibroblastic foci based on the histopathologic differences in the glycosaminoglycan distribution and collagen deposition. In addition, we also aimed at clarifying the stage-specific characteristics by taking into consideration the expression pattern of matrix metalloproteinase and angiogenesis. Lung biopsies of 16 patients with idiopathic pulmonary fibrosis were used. The presence of glycosaminoglycans was detected by Alcian blue staining, and type I collagen was detected by immunohistochemical analysis with a primary antibody specific to the cross-linked carboxyterminal telopeptide of type I collagen. The fibroblastic foci characterized by the expression intensity of Alcian blue and telopeptide of type I collagen were divided into 3 groups, namely, Alcian blue(+)telopeptide of type I collagen(weak), Alcian blue(+)telopeptide of type I collagen(+), and Alcian blue(weak)telopeptide of type I collagen(+); consequently, 3 new stages were defined--stages I, II, and III, respectively. A significant inverse correlation was observed between the area densities of Alcian blue(+) and telopeptide of type I collagen(+) in fibroblastic foci. Stage I was characterized by the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloprotease-2 in fibroblasts and the overlying epithelium of fibroblastic foci, and also the absence of capillary angiogenesis. In contrast, the expression of these proteins was attenuated in stage III, except for that of matrix metalloproteinase-2 in fibroblasts. In stages II and III, capillary angiogenesis was observed. Lymphangiogenesis was undetected in all the 3 stages. Thus, pathologic staging helps understand the roles of the factors involved in tissue remodeling in idiopathic pulmonary fibrosis.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan. yamam@mail.tains.tohoku.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamashita
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Ryoji
authors.initials: R
authors.lastname: Chiba
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Iwama
authors.forename: Fumiko
authors.initials: F
authors.lastname: Date
authors.forename: Naoko
authors.initials: N
authors.lastname: Shibata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kumagai
authors.forename: Juha
authors.initials: J
authors.lastname: Risteli
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sato
authors.forename: Tohru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Masao
authors.initials: M
authors.lastname: Ono
mesh_terms: D000368:Aged; D000423:Alcian Blue / Q000378:metabolism; D016022:Case-Control Studies; D024042:Collagen Type I / Q000378:metabolism; D004396:Coloring Agents / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006025:Glycosaminoglycans / Q000235:genetics / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D004396:Coloring Agents; D006025:Glycosaminoglycans; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D000423:Alcian Blue