Wang Youpei, Wu Xinmei, Wang Qing, Zheng Meiqin, Pang Lingxia
Clinical Examination Center, The Affiliated Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Mol Med Rep. 2017 Jun;15(6):4207-4216. doi: 10.3892/mmr.2017.6535. Epub 2017 May 2.
Delayed healing of skin wounds is one of the outcomes of diabetes mellitus (DM), a condition that affects a significant number of patients worldwide. However, the underlying mechanisms remain unknown. In order to examine proteome alterations in DM, a rat model of type 1 diabetes was developed using streptozotocin injections. The proteomic responses of normal and DM rat skin were analyzed by two‑dimensional electrophoresis, and differentially expressed proteins were identified using a liquid chromatography/mass spectrometry system. DM induced 36 and repressed 41 differentially expressed proteins, respectively. Altered proteins were involved in a number of biological processes, including RNA and protein metabolism, the tricarboxylic acid cycle, glycolysis, cytoskeleton regulation, hydrogen detoxification and calcium‑mediated signal transduction. In addition, overexpression of annexin A2, one of the signaling proteins altered by DM, accelerated the rate of human skin fibroblast cell migration. Application of SP600125, an inhibitor of a key regulator of cell migration c‑Jun N‑terminal kinase (JNK), inhibited the migration of normal cells. By contrast, SP600125 treatment did not inhibit the migration of annexin A2‑overexpressed cells, indicating that annexin A2 may function downstream of JNK. In conclusion, the results of the present study reveal the potential proteomic responses to DM in skin tissues, and demonstrate a positive functional role of annexin A2 in fibroblast cell migration.
皮肤伤口愈合延迟是糖尿病（DM）的后果之一，糖尿病影响着全球大量患者。然而，其潜在机制仍不清楚。为了研究糖尿病中的蛋白质组变化，通过注射链脲佐菌素建立了1型糖尿病大鼠模型。采用二维电泳分析正常和糖尿病大鼠皮肤的蛋白质组反应，并使用液相色谱/质谱系统鉴定差异表达的蛋白质。糖尿病分别诱导了36种差异表达蛋白并抑制了41种差异表达蛋白。改变的蛋白质涉及许多生物学过程，包括RNA和蛋白质代谢、三羧酸循环糖酵解、细胞骨架调节、氢解毒和钙介导的信号转导。此外，膜联蛋白A2（一种因糖尿病而改变的信号蛋白）的过表达加速了人皮肤成纤维细胞的迁移速率。细胞迁移关键调节因子c-Jun氨基末端激酶（JNK）的抑制剂SP600125的应用抑制了正常细胞的迁移。相比之下，SP600125处理并未抑制膜联蛋白A2过表达细胞的迁移，这表明膜联蛋白A2可能在JNK的下游发挥作用。总之，本研究结果揭示了皮肤组织对糖尿病潜在的蛋白质组反应，并证明了膜联蛋白A2在成纤维细胞迁移中具有积极的功能作用。
