title: Expression profiles of collagens, HSP47, TGF-beta1, MMPs and TIMPs in epidermolysis bullosa acquisita.
abstract: Epidermolysis bullosa acquisita (EBA) is a chronic, uncommon, sub-epidermal blistering disease involving the skin and mucous membranes that heals with scar formation and milia. Collagens, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are important components that play an essential role(s) in matrix remodeling during scar formation. However, the possible involvement of these components in EBA-induced scarring is not yet known. In the present study, we examined the expression profile of collagens, collagen-binding heat shock protein 47 (HSP47), MMPs and their inhibitory enzymes, TIMPs, in matrix remodeling during conjunctival scarring. The involvement of TGF-beta1, a fibrogenic factor, was also studied. Compared to the controls, an increased expression of type I collagen, type III collagen and HSP47 was detected in conjunctival biopsy sections of patient with EBA using immunohistochemistry. Similar increase in the expression of type I collagen, type III collagen and HSP47 was noted in conjunctival fibroblasts obtained from the patient with EBA. Up-regulation in the expression of MMP-1 and MMP-14 was also noted in conjunctival fibroblasts isolated from the patient with EBA, while no significant changes in the expression of MMP-3, MMP-8, MMP-9 and MMP-13 were seen. As for TIMPs, conjunctival fibroblasts isolated from the patient with EBA, grown in vitro, exhibited increased expression of TIMP-1, TIMP-2 and TIMP-3, when compared with fibroblasts grown from control conjunctival tissues, although the expression level varies with different molecules of the same family. Additionally, compared to the control conjunctival fibroblasts, an increased expression of TGF-beta1 was detected in fibroblasts isolated from the conjunctival tissues of patient with EBA. This study suggests that there is up-regulation in the production of collagens (type I and III), collagen-binding protein (HSP47), matrix degrading collagenases (MMP-1 and 14), and their inhibitory enzymes (TIMP-1, 2 and 3) during the process of conjunctival matrix remodeling in the patient with EBA. The presented data is preliminary and could serve as a basis for further studies to enhance our understanding about the molecular mechanisms of conjunctival scarring in patients with EBA.
authors.affiliation: Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Razzaque
authors.forename: Suman
authors.initials: S
authors.lastname: Kumari
authors.forename: C Stephen
authors.initials: CS
authors.lastname: Foster
authors.forename: A Razzaque
authors.initials: AR
authors.lastname: Ahmed
mesh_terms: D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D016107:Epidermolysis Bullosa Acquisita / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494660:SERPINH1 protein, human; C508960:TGFB1 protein, human; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D020782:Matrix Metalloproteinases