title: Transcriptomic study of high‑glucose effects on human skin fibroblast cells.
abstract: Skin ulcers are a common complication of diabetes mellitus (DM). Fibroblasts are located within the dermis of skin tissue and can be damaged by diabetes. However, the underlying mechanism of how DM affects fibroblasts remains elusive. To understand the effects of DM on fibroblasts, the current study mimicked DM by high‑glucose (HG) supplementation in the culture medium of human foreskin primary fibroblast cells, and the analysis of transcriptomic changes was conducted. RNA sequencing‑based transcriptome analysis identified that, upon HG stress, 463 genes were upregulated and 351 genes downregulated (>1.5‑fold changes; P<0.05). These altered genes were distributed into 20 different pathways. In addition, gene ontology (GO) analysis indicated that 31 GO terms were enriched. Among the pathways identified, nuclear factor κB (NF‑κB) pathway genes were highly expressed, and the addition of Bay11‑7082, a typical NF‑κB signaling inhibitor, blocked the previously observed alterations in plasminogen activator inhibitor 1 (PAI1), an inflammation marker and frizzled class receptor 8 (FZD8), a Wnt signaling gene, expression that resulted from HG stress. Furthermore, an inhibitor of Wnt signaling diminished the role of Bay11‑7082 in the regulation of PAI1 expression under HG conditions, suggesting that Wnt signaling may function downstream of the NF‑κB pathway to protect fibroblast cells from HG stress. To the best of our knowledge, the current study is the first analysis of transcriptomic responses under HG stress in human fibroblasts. The data provided here may aid the understanding of the molecular mechanisms by which fibroblast cells are damaged in the skin of patients with DM.
authors.affiliation: Function Experiment Teaching Center, Wenzhou Medical University, Wenzhou, Zhejiang 325305, P.R. China.
authors.forename: Lingxia
authors.initials: L
authors.lastname: Pang
authors.affiliation: Clinical Examination Center, The Affiliated Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Youpei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Clinical Examination Center, The Affiliated Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Meiqin
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Function Experiment Teaching Center, Wenzhou Medical University, Wenzhou, Zhejiang 325305, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
authors.affiliation: Operating Room, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Lingjian
authors.initials: L
authors.lastname: Wu
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D012867:Skin / Q000166:cytology; D059467:Transcriptome
chemical_list: D016328:NF-kappa B; D005947:Glucose