Silencing of ERRα gene represses cell proliferation and induces apoptosis in human skin fibroblasts

Estrogen-related receptor (ERR) is an orphan nuclear receptor structurally akin to the estrogen receptor. ERR is expressed in tissues with active energy metabolism and regulates intracellular metabolic functions. Additionally, ERRs are known to be strongly expressed in the epidermis of skin tissue, but their functions are unknown. The present study investigated the function of ERR alpha in human skin fibroblasts. ERR alpha expressed in human dermal fibroblast TIG113 was knocked down using small interfering (si)RNA and gene expression was comprehensively analyzed using microarrays 48 h later. Pathway analysis was performed using Wikipathways on genes exhibiting expression changes of >= 1.5-fold. Expression of cell cycle-related and apoptosis-related genes was compared using reverse transcription-quantitative PCR. After treating TIG113 cells with siERR alpha for 72 h, cell proliferation was assessed using the Cell Counting Kit-8 or a scratch wound healing assay and apoptotic cells were measured using the Poly Caspase Assay Kit. Cell cycle analysis was performed using flow cytometry. The expression of the ERR alpha gene was suppressed by siRNA. The expression of genes associated with cell cycle-related pathways were decreased while that of those associated with apoptosis-related pathways increased. Furthermore, the expression of cell cycle-related genes such as cell division cycle 25C, cyclin E and cyclin B1 was decreased and the expression of apoptosis-related genes such as caspase3 and Fas cell surface death receptor was increased. Cell proliferation was suppressed and the number of apoptotic cells increased similar to 2-fold in ERR alpha-knockdown TIG113 cells. Cell cycle analysis revealed that the number of cells in the Sub-G1 phase increased and that in the S and G(2)/M phases decreased. The present study suggested that ERR alpha is an essential for the survival of human skin fibroblasts.