Department of Urology, Pusan National University Yangsan Hospital, Yangsan 626-870, Korea.
Immune Reconstitution Research Center of Medical Research Institute, Pusan National University College of Medicine, Yangsan 626-870, Korea.
Mar Drugs. 2022 Mar 28;20(4):232. doi: 10.3390/md20040232.
Thymic epithelial cells (TECs) account for the most abundant and dominant stromal component of the thymus, where T cells mature. Oxidative- or cytotoxic-stress associated injury in TECs, a significant and common problem in many clinical settings, may cause a compromised thymopoietic capacity of TECs, resulting in clinically significant immune deficiency disorders or impairment in the adaptive immune response in the body. The present study demonstrated that fish collagen peptides (FCP) increase cell viability, reduce intracellular levels of reactive oxygen species (ROS), and impede apoptosis by repressing the expression of Bax and Bad and the release of cytochrome c, and by upregulating the expression of Bcl-2 and Bcl-xL in cisplatin-treated TECs. These inhibitory effects of FCP on TEC damage occur via the suppression of ROS generation and MAPK (p38 MAPK, JNK, and ERK) activity. Taken together, our data suggest that FCP can be used as a promising protective agent against cytotoxic insults- or ROS-mediated TEC injury. Furthermore, our findings provide new insights into a therapeutic approach for the future application of FCP in the prevention and treatment of various types of oxidative- or cytotoxic stress-related cell injury in TECs as well as age-related or acute thymus involution.
胸腺上皮细胞(TEC)是胸腺中最丰富和最主要的基质成分,T 细胞在此成熟。在许多临床环境中,与氧化或细胞毒性应激相关的 TEC 损伤是一个重大且常见的问题,可能导致 TEC 的胸腺生成能力受损,从而导致临床上明显的免疫缺陷疾病或机体适应性免疫反应受损。本研究表明,鱼胶原蛋白肽(FCP)通过抑制 Bax 和 Bad 的表达以及细胞色素 c 的释放,并上调 Bcl-2 和 Bcl-xL 的表达,增加细胞活力,降低顺铂处理的 TEC 内活性氧(ROS)水平,抑制细胞凋亡。FCP 对 TEC 损伤的这些抑制作用是通过抑制 ROS 生成和 MAPK(p38 MAPK、JNK 和 ERK)活性来实现的。综上所述,我们的数据表明,FCP 可用作一种有前途的保护剂,防止细胞毒性损伤或 ROS 介导的 TEC 损伤。此外,我们的研究结果为未来应用 FCP 预防和治疗 TEC 中各种类型的氧化或细胞毒性应激相关细胞损伤以及与年龄相关或急性胸腺萎缩提供了新的见解。