National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, People's Republic of China.
Biol Reprod. 2020 May 26;102(6):1213-1224. doi: 10.1093/biolre/ioaa022.
S100A4 has been suggested to be a critical regulator of tumor metastasis and is implicated in the progression of inflammation. The aim of this study is to investigate the expression and possible role of S100A4 in epididymitis. Using a mouse model of epididymitis induced by the injection of lipopolysaccharide (LPS) in the deferent duct, we found that LPS administration induced an upregulation of S100a4 transcription (P < 0.05) and a recruitment of S100A4 positive cells in the epididymal interstitium of wild type (WT) mice. Co-immunofluorescence showed that S100A4 was mainly expressed by granulocytes, CD4 lymphocytes, and macrophages. Deficiency of S100A4 reduced epididymal pathological reaction and the mRNA levels of the pro-inflammatory cytokines IL-1β and TNF-α (P < 0.01), suggesting that S100A4 promotes the progression of epididymitis. Furthermore, S100A4 deficiency alleviated the decline of sperm motility and rectified the abnormal expression of sperm membrane protein AMAD3, which suggested that in the progression of epididymitis, S100A4 aggravates the damage to sperm vitality. In addition, both Ki-67 marked cell proliferation and transferase-mediated dUTP-biotin nick end labeling detected cell apoptosis were reduced in S100a4-/- mice compared with WT mice after LPS treatment, indicating that S100A4 promotes both cell proliferation and cell apoptosis in epididymitis. Overall, these results demonstrate that S100A4 promotes the progression of LPS-induced epididymitis and facilitates a decline in sperm vitality, and its function may be related to the process of cell proliferation and apoptosis during inflammation.
S100A4 被认为是肿瘤转移的关键调节因子，并与炎症的进展有关。本研究旨在探讨 S100A4 在附睾炎中的表达及其可能的作用。我们使用向输精管中注射脂多糖（LPS）诱导的小鼠附睾炎模型，发现 LPS 给药诱导 S100a4 转录上调（P<0.05），并导致野生型（WT）小鼠附睾间质中 S100A4 阳性细胞募集。共免疫荧光显示 S100A4 主要由粒细胞、CD4 淋巴细胞和巨噬细胞表达。S100A4 缺失减少了附睾的病理反应和促炎细胞因子 IL-1β 和 TNF-α 的 mRNA 水平（P<0.01），表明 S100A4 促进了附睾炎的进展。此外，S100A4 缺失减轻了精子活力的下降，并纠正了精子膜蛋白 AMAD3 的异常表达，这表明在附睾炎的进展过程中，S100A4 加重了精子活力的损伤。此外，与 LPS 处理后的 WT 小鼠相比，S100a4-/- 小鼠的 Ki-67 标记的细胞增殖和转铁蛋白介导的 dUTP-生物素切口末端标记检测到的细胞凋亡均减少，表明 S100A4 促进了附睾炎中的细胞增殖和细胞凋亡。总的来说，这些结果表明 S100A4 促进了 LPS 诱导的附睾炎的进展，并导致精子活力下降，其功能可能与炎症过程中的细胞增殖和凋亡过程有关。
