Research Institute of Medical Science, Konkuk University School of Medicine, 82 Gugwon-daero, Chungju, 27376, Korea.
Department of Plastic and Reconstructive Surgery, Konkuk University School of Medicine, Konkuk University Chungju Hospital, 82 Gugwon-daero, Chungju, 27376, Korea.
Arch Dermatol Res. 2019 Nov;311(9):711-719. doi: 10.1007/s00403-019-01961-6. Epub 2019 Aug 5.
We conducted this experimental study to analyze the relationship between sphingosine-1-phosphate (S1P)-induced mitogen-activated protein (MAP) kinase pathways and keloid formation. We collected samples of the normal tissue and the keloid tissue from 10 normal healthy individuals and 12 patients with keloid scars, respectively. Then, we compared the level of sphingosine-1-phosphate receptor (S1PR1/S1PR2) mRNA/protein expression between the normal tissue and the keloid tissue. Moreover, we also compared the level of S1PR protein expression, that of S1P-induced COL1A1 (collagen Type I, α-1 chain) expression, that of S1P-induced JNK/ERK phosphorylation, that of S1P-induced COL1A1 expression following the treatment with 30 μM PD98059 (ERK inhibitor) or 30 μM SP600125 (JNK inhibitor) and that of S1P-induced COL1A1 expression following the treatment with W146 (S1PR1 inhibitor) or JTE013 (S1PR2 inhibitor) between the normal fibroblasts and the keloid fibroblasts. We found that the level of S1PR1/S1PR2 mRNA/protein expression was significantly higher in the keloid tissue as compared with the normal tissue. Our results also showed that the level of S1P-induced COL1A1 expression and that of S1P-induced JNK/ERK phosphorylation were significantly higher in the keloid fibroblasts as compared with the normal ones (P < 0.05). Furthermore, there were significant decreases in the level of S1P-induced COL1A1 expression when the keloid fibroblasts were treated with 30 μM SP600125 or 30 μM PD98059 and that of S1P-induced COL1A1 expression when the treated with 100 nM W146 or 100 nM JTE013 (P < 0.05). Our results indicate that S1P-induced signal transduction is associated with increased collagen synthesis via S1PR-mediated signaling pathways in the keloid tissue.
我们进行了这项实验研究，以分析神经鞘氨醇-1-磷酸（S1P）诱导的丝裂原激活蛋白（MAP）激酶途径与瘢痕疙瘩形成之间的关系。我们分别从 10 名正常健康个体和 12 名瘢痕疙瘩患者的正常组织和瘢痕疙瘩组织中收集样本。然后，我们比较了正常组织和瘢痕疙瘩组织中鞘氨醇-1-磷酸受体（S1PR1/S1PR2）mRNA/蛋白表达水平。此外，我们还比较了 S1P 诱导的 COL1A1（胶原蛋白 I，α-1 链）表达、S1P 诱导的 JNK/ERK 磷酸化、30μM PD98059（ERK 抑制剂）或 30μM SP600125（JNK 抑制剂）处理后 S1P 诱导的 COL1A1 表达以及 W146（S1PR1 抑制剂）或 JTE013（S1PR2 抑制剂）处理后 S1P 诱导的 COL1A1 表达水平之间的差异。我们发现，与正常组织相比，瘢痕疙瘩组织中 S1PR1/S1PR2 mRNA/蛋白表达水平显著升高。我们的结果还表明，与正常成纤维细胞相比，瘢痕疙瘩成纤维细胞中 S1P 诱导的 COL1A1 表达水平和 S1P 诱导的 JNK/ERK 磷酸化水平显著升高（P<0.05）。此外，当用 30μM SP600125 或 30μM PD98059 处理瘢痕疙瘩成纤维细胞时，S1P 诱导的 COL1A1 表达水平显著降低，当用 100nM W146 或 100nM JTE013 处理时，S1P 诱导的 COL1A1 表达水平也显著降低（P<0.05）。我们的结果表明，S1P 诱导的信号转导与瘢痕疙瘩组织中 S1PR 介导的信号通路导致胶原蛋白合成增加有关。
