Differentially expressed genes affected by CSRNP1 overexpression in human-derived vaginal fibroblasts

Pelvic organ prolapse (POP) is a group of diseases caused by extracellular matrix (ECM) degradation in the pelvic supportive tissues. Cysteine and serine rich nuclear protein 1 (CSRNP1) is involved in cell proliferation and survival regulation, and reportedly facilitates collagen breakdown in human chondrocytes. We here uncovered CSRNP1 as a key driver on collagen degradation in human-derived vaginal fibroblasts. Apoptosis of POP patient-derived vaginal fibroblasts was suppressed after knocking down CSRNP1. Silencing of CSRNP1 inhibited hydrogen peroxide (H2O2)-triggered apoptosis, ROS generation and collagen loss in normal vaginal fibroblasts. In line with this, CSRNP1 overexpression led to proliferation inhibition, apoptosis and collagen degradation in normal subject-derived vaginal fibroblasts. Silencing of CSRNP1 also reduced the expression of cell senescence markers p21 and ?-H2Ax (the histone H2Ax phosphorylated at Ser139), as well as curbed collagen breakdown in normal vaginal fibroblasts caused by a DNA damage agent etoposide. Transcriptomic analysis showed that differentially expressed genes affected by CSRNP1 overexpression in normal vaginal fibroblasts were mainly enriched in the Wnt signaling pathway, which was crucial for the onset and progression of POP. Silencing of CSRNP1 upregulated the expression of nuclear ß-catenin and induced nuclear translocation of ß-catenin in H2O2-induced normal vaginal fibroblast. Furthermore, collagen deposition caused by CSRNP1 knockdown was curbed after treatment with a Wnt pathway inhibitor DKK1. Our study indicates that the CSRNP1 may be involved in POP progression through the Wnt signaling, which provides a potential therapeutic strategy for POP. Overall design: To investigate the effect and underlying mechanisms of CSRNP1 on collagen degradation in human-derived vaginal fibroblasts, we isolated vaginal fibroblasts from normal-derived anterior vaginal wall tissues in which CSRNP1 was highly expressed by lentivirus overexpression system. We then performed gene expression profiling analyses using data from mRNA-seq for vaginal fibroblasts of CSRNP1 overexpression versus controls.