Department of Dermatology, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China.
Institute of Biomedical Innovation and School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China.
J Proteomics. 2024 Apr 30;298:105155. doi: 10.1016/j.jprot.2024.105155. Epub 2024 Mar 8.
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.
赖氨酸琥珀酰化（Ksucc）是一种新发现的翻译后修饰，与许多疾病有关。本研究探讨了 Ksucc 在肥厚性瘢痕（HS）发病机制中的作用。通过免疫印迹法测量人皮肤中的 Ksucc 存在情况。Ksucc 存在于 25 至 250 kDa 的许多皮肤蛋白中，HS 皮肤中的 Ksucc 水平高于正常皮肤。采用免疫亲和法结合 LC-MS/MS 技术对人皮肤的第一个琥珀酰基组进行了特征分析，鉴定了 79 种蛋白质中的 159 个 Ksucc 位点。在这些蛋白质中，与正常皮肤相比，HS 中有 29 种蛋白质的 38 个琥珀酰化位点增加，但没有琥珀酰化位点减少。进行平行反应监测测定以验证琥珀酰基组的结果，结果表明参与 HS 发病机制的核心蛋白聚糖和胶原蛋白中 Ksucc 的水平在 HS 中高于正常皮肤。此外，增加 Ksucc 的水平可增强人皮肤成纤维细胞的增殖，并上调纤维化标志物（α-SMA、COL1 和 COL3）的表达。我们的研究结果为 Ksucc 在肥厚性瘢痕形成中的功能作用提供了全局见解。
