Upregulation of Cytokines Midkine and Pleiotrophin in Keloids
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Keloids are benign proliferative scars that are exaggerated responses to cutaneous wound healing. They can be painful and/or pruritic, and commonly affect the chest, upper back, shoulders, and earlobes. Keloids often affect skin of color; most keloid patients are of African, Hispanic, or Asian descent. Although keloids are heavily implicated in fibrosis, there remain gaps in our understanding of keloid pathogenesis and our elucidation of potential biomarkers. The goal of this project was to identify novel molecules upregulated in keloids in order to identify uncharacterized mechanisms underlying keloid pathogenesis. Matched sets of keloid tissue and perilesional normal tissue were obtained from three keloid patients recruited from the outpatient dermatology clinics of Parkland Hospital and UT Southwestern Medical Center. Whole transcriptome sequencing comparing keloid tissue to perilesional normal tissue showed 344 genes with differential expression across the three sample pairings. Of note were Midkine (MDK) and Pleiotrophin (PTN), which were upregulated 30 fold and 10 fold respectively. MDK and PTN are cytokine signaling molecules known to play a role in wound healing, mitogenicity, and inflammation. They are upregulated in several cancers, and higher expression generally indicates poor prognosis. Keloids have been implicated in cancer pathogenesis, and prior research has shown that human skin keloid fibroblasts display bioenergetics of cancer cells (Vincent AS, 2008). Because MDK and PTN were upregulated in whole keloid tissue, we hypothesized that MDK and PTN would be upregulated in primary keloid fibroblasts in vitro versus primary normal skin fibroblasts in vitro. We performed RT-PCR on RNA obtained from keloid fibroblasts and normal fibroblasts grown in vitro, using MDK, PTN, and GAPDH (positive control) primers, and water serving as a negative control. Results showed that keloid fibroblasts did not have significant increased expression of MDK and PTN at the RNA level compared to normal skin fibroblasts grown in vitro. It is possible that some other component of the keloid microenvironment, such as keratinocytes, endothelial cells, or inflammatory cells may be inducing upregulation of MDK and PTN in whole keloid tissue in vivo. Further work on this project involves performing Western blots on keloid fibroblasts and normal fibroblasts grown in vitro to determine whether MDK and PTN are upregulated at the protein level. In addition, in situ hybridization experiments for MDK and PTN on keloid sections will enable us to determine which cell type(s) are making MDK and PTN in keloid tissue.
The 58th Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 21, 2020, 3-6 p.m., D1.600)
Marella, P., Tran, A., & Glass, D. A., II (2020, January 21). Upregulation of cytokines midkine and pleiotrophin in keloids. Poster session presented at the 58th Annual Medical Students Research Forum, Dallas, TX. Retrieved from https://hdl.handle.net/2152.5/8268