The Interaction of PELP1 With FHL2 Contributes to Ectopic Endometrial Stromal Cell Proliferation, Angiogenesis, and Inflammation in Endometriosis

The Interaction of PELP1 With FHL2 Contributes to Ectopic Endometrial Stromal Cell Proliferation, Angiogenesis, and Inflammation in Endometriosis Yanmei Cheng Department of Gynaecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Search for more papers by this authorShiwei Li Department of Throat Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Search for more papers by this authorLei Zhao Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Search for more papers by this authorGailing Li Department of Gynaecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Search for more papers by this authorCorresponding Author Huirong Shi Department of Gynaecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Correspondence: Huirong Shi ([email protected]; [email protected]) Search for more papers by this authorYanmei Cheng Department of Gynaecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Search for more papers by this authorShiwei Li Department of Throat Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Search for more papers by this authorLei Zhao Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Search for more papers by this authorGailing Li Department of Gynaecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Search for more papers by this authorCorresponding Author Huirong Shi Department of Gynaecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Correspondence: Huirong Shi ([email protected]; [email protected]) Search for more papers by this authorABSTRACT Endometriosis (EMS), a multifactorial and chronic benign gynecological disease characterized by ectopic endometrial growth, remains poorly understood in its pathogenesis. Proline, glutamic acid, leucine-rich protein 1 (PELP1), implicated in various diseases, has not been studied in EMS. Here, we investigated the functional role and molecular mechanisms of PELP1 in EMS progression. Using ectopic and eutopic endometrial tissues from EMS patients, we showed that PELP1 was significantly upregulated in ectopic lesions. Knockdown of PELP1 in primary ectopic endometrial stromal cells (Ec-ESCs) and the mouse model inhibited proliferation, angiogenesis, and inflammation. Mechanistically, PELP1 interacted with FHL2 to potentiate transcriptional activation of downstream factors, such as CCND1, CCND2, CDK6, ANG, CCL2, and MMP3. These findings demonstrate that PELP1 promotes EMS progression and highlight its potential as a novel therapeutic target. Conflicts of Interest The authors declare no conflicts of interest. Data Availability Statement The data of this study could be accessible from the corresponding author upon reasonable request. Supporting Information | Filename | Description | |---|---| | cbin70096-sup-0001-Supplementary_Materials.docx324.6 KB | Figure S1: (A) Ectopic endometrium endometrial stromal cells (Ec-ESCs) were isolated from fresh Ec tissues, and then the cell morphology of ectopic endometrial stromal cells (Ec-ESCs) was examined. Scale bars: 200 μm or 100 μm. (B) For Ec-ESCs identification, immunofluorescence (IF) staining was used to detect the expression of vimentin and CK7. Scale bars: 50 μm. (C) Eutopic endometrium endometrial stromal cells (Eu-ESCs) were infected with shNC or shPELP1 lentivirus, 72 h post-infection, Western blot analysis and quantification of the protein level of PELP1. (D) CCK8 assay was used to determine the viability of Eu-ESCs. For (A)-(C), n=3 biological replicates. 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