2. Academic Validation
  3. Enhancement of Ndrg2 promotes hypertrophic scar fibrosis by regulating PI3K/AKT signaling pathway

Enhancement of Ndrg2 promotes hypertrophic scar fibrosis by regulating PI3K/AKT signaling pathway

  • Cell Signal. 2025 May:129:111659. doi: 10.1016/j.cellsig.2025.111659.
Boya Yu 1,  Yalei Cao 2,  Pianpian Lin 3,  Lixia Zhang 4,  Minliang Chen 5
Affiliations

Affiliations

  • 1 Department of Plastic and Reconstructive Surgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; Chinese PLA Medical School, Beijing 100853, China. Electronic address: yby0507@163.com.
  • 2 Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
  • 3 Department of Plastic and Reconstructive Surgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; Chinese PLA Medical School, Beijing 100853, China.
  • 4 Department of Plastic and Reconstructive Surgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; Chinese PLA Medical School, Beijing 100853, China. Electronic address: vivian-0506@163.com.
  • 5 Department of Plastic and Reconstructive Surgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; Chinese PLA Medical School, Beijing 100853, China. Electronic address: chenml@sohu.com.
PMID: 39956247 DOI: 10.1016/j.cellsig.2025.111659
Abstract

Hypertrophic scar (HTS) is a prevalent chronic inflammatory skin disorder characterized by abnormal proliferation and extracellular matrix deposition. N-Myc downstream regulated gene 2 (Ndrg2) is a cell stress response gene related to cell proliferation, differentiation and various fibrotic diseases. However, the role of Ndrg2 in HTS is unknown and warrants further investigation. In this study, we confirmed that the expression of Ndrg2 was increased in HTS of human and a bleomycin-induced fibrosis mouse model. We then used Ndrg2 knockout mice and found Ndrg2 deletion could significantly reduce the synthesis of collagen and alleviate skin fibrosis. In addition, the proliferation and migration of Ndrg2-interfered HTS-derived fibroblasts decreased and those of Ndrg2-overexpressed normal skin-derived fibroblasts increased. Further, by western blot analysis, we verified that the expression of phosphorylated-PI3K, PI3K, phosphorylated-AKT and Akt were all increased after Ndrg2 overexpressed in normal skin-derived fibroblasts. Moreover, PI3K Inhibitor (LY294002) administration significantly rescued the effect of Ndrg2 overexpression on skin fibrosis. In summary, our results demonstrated that Ndrg2 could promote HTS fibrosis by mediating PI3K/Akt signaling pathway. Our data suggest that Ndrg2 may be a promising therapeutic target for HTS.

Keywords

Fibroblast; Hypertrophic scar; Ndrg2; Skin fibrosis.

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