hTERT peptide fragment GV1001 demonstrates radioprotective and antifibrotic effects through suppression of TGF‑β signaling

Chen,Wei; Shin,Ki‑Hyuk; Kim,Sangjae; Shon,Won‑Jun; Kim,Reuben  H.; Park,No‑Hee; Kang,Mo  K.

doi:10.3892/ijmm.2018.3566

hTERT peptide fragment GV1001 demonstrates radioprotective and antifibrotic effects through suppression of TGF‑β signaling

Authors:
- Wei Chen
- Ki‑Hyuk Shin
- Sangjae Kim
- Won‑Jun Shon
- Reuben H. Kim
- No‑Hee Park
- Mo K. Kang
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Affiliations: The Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, CA 90095, USA, TELOID Inc, Los Angeles, CA 90024, USA, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea
Published online on: March 14, 2018 https://doi.org/10.3892/ijmm.2018.3566
Pages: 3211-3220
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

GV1001 is a 16‑amino acid peptide derived from the human telomerase reverse transcriptase (hTERT) protein (616‑626; EARPALLTSRLRFIPK), which lies within the reverse transcriptase domain. Originally developed as an anticancer vaccine, GV1001 demonstrates diverse cellular effects, including anti‑inflammatory, tumor suppressive and antiviral effects. In the present study, the radioprotective and antifibrotic effects of GV1001 were demonstrated through suppressing transforming growth factor‑β (TGF‑β) signaling. Proliferating human keratinocytes underwent premature senescence upon exposure to ionizing radiation (IR), however, treatment of cells with GV1001 allowed the cells to proliferate and showed a reduction in senescent phenotype. GV1001 treatment notably increased the levels of Grainyhead‑like 2 and phosphorylated (p‑)Akt (Ser473), and reduced the activation of p53 and the level of p21/WAF1 in irradiated keratinocytes. It also markedly suppressed the level of TGF‑β signaling molecules, including p‑small mothers against decapentaplegic (Smad)2/3 and Smad4, and TGF‑β target genes, including zinc finger E‑box binding homeobox 1, fibronectin, N‑cadharin and Snail, in irradiated keratinocytes. Furthermore, GV1001 suppressed TGF‑β signaling in primary human fibroblasts and inhibited myofibroblast differentiation. Chromatin immunoprecipitation revealed that GV1001 suppressed the binding of Smad2 on the promoter regions of collagen type III α1 chain (Col3a1) and Col1a1. In a dermal fibrosis model in vivo, GV1001 treatment notably reduced the thickness of fibrotic lesions and the synthesis of Col3a1. These data indicated that GV1001 ameliorated the IR‑induced senescence phenotype and tissue fibrosis by inhibiting TGF‑β signaling and may have therapeutic effects on radiation‑induced tissue damage.

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