Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
mSystems. 2023 Dec 21;8(6):e0090423. doi: 10.1128/msystems.00904-23. Epub 2023 Oct 24.
Chronic or repeated infection of the female upper genital tract by can lead to severe fibrotic sequelae, including tubal factor infertility and ectopic pregnancy. However, the molecular mechanisms underlying this effect are unclear. In this report, we define a transcriptional program specific to infection of the upper genital tract, identifying tissue-specific induction of host YAP-a pro-fibrotic transcriptional cofactor-as a potential driver of infection-mediated fibrotic gene expression. Furthermore, we show that infected endocervical epithelial cells stimulate collagen production by fibroblasts and implicate chlamydial induction of YAP in this effect. Our results define a mechanism by which infection mediates tissue-level fibrotic pathology via paracrine signaling and identify YAP as a potential therapeutic target for the prevention of -associated scarring of the female genital tract.
沙眼衣原体慢性或反复感染女性上生殖道可导致严重的纤维化后遗症，包括输卵管性不孕和宫外孕。然而，其具体的分子机制尚不清楚。在本研究中，我们定义了一个特定于沙眼衣原体感染上生殖道的转录程序，鉴定了宿主 YAP（一种促纤维化的转录共因子）在上生殖道组织中的特异性诱导，这可能是感染介导纤维化基因表达的一个潜在驱动因素。此外，我们还发现感染的宫颈上皮细胞刺激成纤维细胞产生胶原蛋白，并表明沙眼衣原体诱导 YAP 在这一过程中发挥作用。我们的研究结果定义了感染通过旁分泌信号介导组织水平纤维化病理的机制，并鉴定 YAP 作为预防女性生殖道沙眼衣原体相关瘢痕形成的潜在治疗靶点。
