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  2. Global proteomic analysis reveals lysine succinylation is involved in the pathogenesis of hypertrophic scar

Global proteomic analysis reveals lysine succinylation is involved in the pathogenesis of hypertrophic scar

  • J Proteomics. 2024 Mar 7:105155. doi: 10.1016/j.jprot.2024.105155.
Keqing Qiu 1 Yan Tian 2 Chunyan Guo 1 Ougen Liu 1 Yan Shi 3 Dewu Liu 4 Tao Luo 5
Affiliations

Affiliations

  • 1 Department of Dermatology, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China.
  • 2 Institute of Biomedical Innovation and School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China.
  • 3 Department of Plastic, Medical Center of Burn Plastic and Wound Repair, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China.
  • 4 Department of Plastic, Medical Center of Burn Plastic and Wound Repair, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address: dewuliu@126.com.
  • 5 Institute of Biomedical Innovation and School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China. Electronic address: luotao@ncu.edu.cn.
Abstract

Lysine succinylation (Ksucc) is a recently identified posttranslational modification that is involved in many diseases. This study examined the role of Ksucc in the pathogenesis of hypertrophic scar (HS). The presence of Ksucc in human skin was measured by immunoblotting. Ksucc occurs in many skin proteins ranging from 25 to 250 kDa, and higher levels of Ksucc are found in HS skin than in normal skin. An immunoaffinity approach coupled with LC-MS/MS was used to characterize the first succinylome of human skin, and 159 Ksucc sites in 79 proteins were identified. Among these, there were 38 increased succinylated sites in 29 proteins but no decreased succinylated sites in HS compared with normal skin. A parallel reaction monitoring assay was performed to validate the results of the succinylome and showed that the levels of Ksucc in decorin and collagens, which are involved in the pathogenesis of HS, were increased in HS than in normal skin. In addition, increasing the level of Ksucc enhanced cell proliferation and upregulated the expression of fibrosis markers (α-SMA, COL1, and COL3) in human skin fibroblasts. Our results provide global insights into the functional role of Ksucc in hypertrophic scarring.

Keywords

Fibrosis; Human skin; Hypertrophic scar; Lysine succinylation; Post-translational modification.

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