Co-localization of LTBP-2 with FGF-2 in fibrotic human keloid and hypertrophic scar

Sideek, Mohamed A.; Teia, Abdulrahman; Kopecki, Zlatko; Cowin, Allison J.; Gibson, Mark A.

doi:10.1007/s10735-015-9645-0

Original Paper
Published: 07 December 2015

Co-localization of LTBP-2 with FGF-2 in fibrotic human keloid and hypertrophic scar

Mohamed A. Sideek^1,2,
Abdulrahman Teia¹,
Zlatko Kopecki³,
Allison J. Cowin³ &
Mark A. Gibson¹

Journal of Molecular Histology volume 47, pages 35–45 (2016)Cite this article

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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.

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Discipline of Anatomy and Pathology, School of Medicine, University of Adelaide, Adelaide, SA, 5005, Australia
Mohamed A. Sideek, Abdulrahman Teia & Mark A. Gibson
Department of Biomedical Sciences, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, 25200, Kuantan, Pahang, Malaysia
Mohamed A. Sideek
Regenerative Medicine, Mawson Institute, University of South Australia, Adelaide, SA, 5095, Australia
Zlatko Kopecki & Allison J. Cowin

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Mohamed A. Sideek
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Abdulrahman Teia
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Zlatko Kopecki
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Allison J. Cowin
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Mark A. Gibson
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Correspondence to Mark A. Gibson.

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Sideek, M.A., Teia, A., Kopecki, Z. et al. Co-localization of LTBP-2 with FGF-2 in fibrotic human keloid and hypertrophic scar. J Mol Hist 47, 35–45 (2016). https://doi.org/10.1007/s10735-015-9645-0

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Received: 02 September 2015
Accepted: 25 November 2015
Published: 07 December 2015
Issue Date: February 2016
DOI: https://doi.org/10.1007/s10735-015-9645-0

Keywords

LTBP-2
FGF-2
Fibrosis
Keloid
Hypertrophic scar