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Biomedicines 2015, 3(1), 110-123; doi:10.3390/biomedicines3010110

Expression of Hepatocyte Growth Factor-Like Protein in Human Wound Tissue and Its Biological Functionality in Human Keratinocytes

1
Cardiff China Medical Research Collaborative (CCMRC), Cardiff University–Peking University Cancer Institute, Cardiff University–Capital Medical University Joint Centre Biomedical Research, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK
2
Department of Wound Healing and Welsh Wound Innovation Centre, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK
*
Author to whom correspondence should be addressed.
Received: 29 June 2014 / Revised: 29 September 2014 / Accepted: 27 January 2015 / Published: 4 February 2015
(This article belongs to the Special Issue New aspects of the Hepatocyte Growth Factor/c-Met System)
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Abstract

Hepatocyte growth factor-like protein (HGFl) and its receptor, Recepteur d'Origine Nantais (RON), have been implicated in the development of wound chronicity. HGFl and RON expression was detected in acute wound tissue, chronic wound tissue and in normal skin using quantitative polymerase chain reaction (Q-PCR). HGFl and RON expression was also assessed in chronic healing and chronic non-healing wound tissues using Q-PCR and immunohistochemical staining. Expression was similarly detected in the HaCaT immortalized human keratinocyte cell line using reverse transcription polymerase chain reaction (RT-PCR). rhHGFl was used to assess the impact of this molecule on HaCaT cell functionality using in vitro growth assays and electric cell-substrate impendence sensing (ECIS) migration assays. HGFl and RON transcript expression were significantly increased in acute wound tissue compared to chronic wound tissue and were also elevated, though non-significantly, in comparison to normal skin. Minimal expression was seen in both healing and non-healing chronic wounds. Treatment of HaCaT cells with rhHGFl had no effect on growth rates but did enhance cell migration. This effect was abolished by the addition of a phospholipase C gamma (PLCγ) small molecule inhibitor. The increased expression of HGFl and RON in acute, healing wounds and the pro-migratory effect of HGFl in an in vitro human keratinocyte model, may indicate a role for HGFl in active wound healing. View Full-Text
Keywords: hepatocyte growth factor-like (HGFl); macrophage stimulating protein (MSP); wound healing; human keratinocyte; HaCaT hepatocyte growth factor-like (HGFl); macrophage stimulating protein (MSP); wound healing; human keratinocyte; HaCaT
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Glasbey, J.C.; Sanders, A.J.; Bosanquet, D.C.; Ruge, F.; Harding, K.G.; Jiang, W.G. Expression of Hepatocyte Growth Factor-Like Protein in Human Wound Tissue and Its Biological Functionality in Human Keratinocytes. Biomedicines 2015, 3, 110-123.

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