Department of Obstetrics and Gynecology, 74566The First Affiliated Hospital of Soochow University, Suzhou city, Jiangsu Province, PR China.
Cell Transplant. 2021 Jan-Dec;30:9636897211002762. doi: 10.1177/09636897211002762.
Telocytes (TCs), which are a recently discovered interstitial cell type present in various organs and tissues, perform multiple biological functions and participate in extensive crosstalk with neighboring cells. Endometriosis (EMs) is a gynecological disease characterized by the presence of viable endometrial debris and impaired macrophage phagocytosis in the peritoneal environment. Here, CD34/vimentin-positive TCs were co-cultured with RAW264.7 cells . M1/M2 differentiation-related markers were detected; phagocytosis, energy metabolism, proliferation, apoptosis, and pathway mechanisms were studied; and the mitochondrial membrane potential (ΔΨm) was measured. Furthermore, in an EMs mouse model, the differentiation of macrophages in response to treatment with TC-conditioned medium (TCM) was studied. The results showed that upon co-culture with TCM, RAW264.7 cells differentiated more toward the M1 phenotype with enhancement of phagocytosis, increase in energy metabolism and proliferation owing to reduced the loss of ΔΨm, and suppression of dexamethasone-induced apoptosis. Further, along with the activation of NF-κB, Bcl-2 and Bcl-xl, the expression of Bax, cleaved-caspase9, and cleaved-caspase3 reduced in RAW264.7 cells. In addition, the M1 subtype was found to be the dominant phenotype among tissue and peritoneal macrophages in the EMs model subjected to TCM treatment. In conclusion, TCs enhanced M1 differentiation and phagocytosis while inhibiting apoptosis via the activation of NF-κB in macrophages, which potentially inhibited the onset of EMs. Our findings provide a potential research target and the scope for developing a promising therapeutic strategy for EMs.
间质细胞（TCs）是一种新发现的存在于各种器官和组织中的间质细胞类型，具有多种生物学功能，并与邻近细胞广泛相互作用。子宫内膜异位症（EMs）是一种妇科疾病，其特征是腹腔环境中存在有活力的子宫内膜碎片和巨噬细胞吞噬功能受损。在这里，CD34/vimentin 阳性 TCs 与 RAW264.7 细胞共培养。检测 M1/M2 分化相关标志物；研究吞噬作用、能量代谢、增殖、凋亡和通路机制；并测量线粒体膜电位（ΔΨm）。此外，在 EMs 小鼠模型中，研究了巨噬细胞对 TC 条件培养基（TCM）治疗的反应。结果表明，与 TCM 共培养后，RAW264.7 细胞向 M1 表型分化更多，吞噬作用增强，能量代谢和增殖增加，这是由于 ΔΨm 的丧失减少，以及地塞米松诱导的凋亡受到抑制。此外，随着 NF-κB 的激活，Bcl-2 和 Bcl-xl 的表达增加，Bax、cleaved-caspase9 和 cleaved-caspase3 的表达减少在 RAW264.7 细胞中。此外，在接受 TCM 治疗的 EMs 模型中，组织和腹腔巨噬细胞中发现 M1 亚型是主要表型。总之，TCs 通过激活巨噬细胞中的 NF-κB 增强 M1 分化和吞噬作用，同时抑制凋亡，从而潜在抑制 EMs 的发生。我们的研究结果为子宫内膜异位症的治疗提供了一个潜在的研究靶点和有前途的治疗策略的范围。
