Downregulation of Epac Reduces Fibrosis and Induces Apoptosis Through Akt Signaling in Human Keloid Fibroblasts

Wenchang Lv, Shengxuan Liu, Qi Zhang, Zhen Yi, Xiaoyong Bao, Youping Feng, Yuping Ren

Research output: Contribution to journalArticlepeer-review

Abstract

Background: A keloid is a type of pathological scar often caused by abnormal tissue repair after a skin injury and is more common in genetically susceptible individuals. cAMP is a universal second messenger and regulates critical physiological processes, including calcium homeostasis, secretion, cell fate, and gene transcription, by affecting the expression of the exchange protein directly activated by cAMP (Epac). Epac has two isoforms, Epac1 (cAMP-GEF-1) and Epac2 (cAMP-GEF-II), which show varying expression levels depending on the tissue and cell type. The expression of Epac1 in keloids has not yet been investigated. Materials and methods: Keloid tissue and normal dermal skin tissue were analyzed by hematoxylin and eosin staining and immunofluorescence. Primary human keloid fibroblasts (HKFs) and human normal dermal fibroblasts were studied using immunofluorescence, wound healing tests, reverse transcription polymerase chain reaction, and western blot analysis with different concentrations of the Epac1 inhibitor ESI-09. Results: Downregulation of Epac was performed using ESI-09, a specific Epac inhibitor. The proliferation and migration capacities of HKFs and human normal dermal fibroblasts showed an ESI-09 concentration-dependent decrease. Furthermore, the apoptosis rates were significantly different between fibroblasts treated with ESI-09 and control fibroblasts. In addition, the phosphorylation level of Akt was significantly decreased, indicating that ESI-09 reduces fibrosis and induces apoptosis through Akt signaling in HKFs. Conclusions: Our results illustrate the role of Epac1 in regulating fibroblast function during keloid pathogenesis and indicate that Epac1 may be a potential therapeutic target in keloid treatment.

Original languageEnglish (US)
Pages (from-to)306-316
Number of pages11
JournalJournal of Surgical Research
Volume257
DOIs
StatePublished - Jan 2021

Keywords

  • Akt
  • ESI-09
  • Epac1
  • Keloid

ASJC Scopus subject areas

  • Surgery

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