title: Co-localization of LTBP-2 with FGF-2 in fibrotic human keloid and hypertrophic scar.
abstract: We have recently shown that Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) has a single high-affinity binding site for fibroblast growth factor-2 (FGF-2) and that LTBP-2 blocks FGF-2 induced cell proliferation. Both proteins showed strong co-localisation within keloid skin from a single patient. In the current study, using confocal microscopy, we have investigated the distribution of the two proteins in normal and fibrotic skin samples including normal scar tissue, hypertrophic scars and keloids from multiple patients. Consistently, little staining for either protein was detected in normal adult skin and normal scar samples but extensive co-localisation of the two proteins was observed in multiple examples of hypertrophic scars and keloids. LTBP-2 and FGF-2 were co-localised to fine fibrous elements within the extracellular matrix identified as elastic fibres by immunostaining with anti-fibrillin-1 and anti-elastin antibodies. Furthermore, qPCR analysis of RNA samples from multiple patients confirmed dramatically increased expression of LTBP-2 and FGF-2, similar TGF-beta 1, in hypertrophic scar compared to normal skin and scar tissue. Overall the results suggest that elevated LTBP-2 may bind and sequester FGF-2 on elastic fibres in fibrotic tissues and modulate FGF-2's influence on the repair and healing processes.
authors.affiliation: Discipline of Anatomy and Pathology, School of Medicine, University of Adelaide, Adelaide, SA, 5005, Australia.|Department of Biomedical Sciences, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, 25200, Kuantan, Pahang, Malaysia.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Sideek
authors.affiliation: Discipline of Anatomy and Pathology, School of Medicine, University of Adelaide, Adelaide, SA, 5005, Australia.
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Teia
authors.affiliation: Regenerative Medicine, Mawson Institute, University of South Australia, Adelaide, SA, 5095, Australia.
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Kopecki
authors.affiliation: Regenerative Medicine, Mawson Institute, University of South Australia, Adelaide, SA, 5095, Australia.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Cowin
authors.affiliation: Discipline of Anatomy and Pathology, School of Medicine, University of Adelaide, Adelaide, SA, 5005, Australia. mark.gibson@adelaide.edu.au.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Gibson
mesh_terms: D000293:Adolescent; D000328:Adult; D001665:Binding Sites; D016022:Case-Control Studies; D017439:Cicatrix, Hypertrophic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004547:Elastic Tissue / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007627:Keloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D062326:Re-Epithelialization / Q000502:physiology; D015398:Signal Transduction; D012867:Skin / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D054392:Adipokines
chemical_list: D004549:Elastin; D000071838:Fibrillin-1; D000071837:Fibrillins; D016222:Fibroblast Growth Factor 2; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; D053773:Transforming Growth Factor beta1; C000605722:FBN1 protein, human; D054392:Adipokines; C509035:LTBP2 protein, human
keywords: FGF-2; Fibrosis; Hypertrophic scar; Keloid; LTBP-2