The role of phoenixin in the proliferation and migration of ectopic epithelial cells in vitro

• Published in: Biochemical and biophysical research communications Vol. 646; pp. 44 - 49
• Main Authors: Kulinska, Karolina Iwona, Białas, Piotr, Dera-Szymanowska, Anna, Billert, Maria, Kotwicka, Małgorzata, Szymanowski, Krzysztof, Wołun-Cholewa, Maria
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.02.2023
• Subjects: Basic Medicine; Cell and Molecular Biology; Cell Proliferation; Cell- och molekylärbiologi; Endometrios; Endometriosis; Epithelial Cells - metabolism; Female; GPR173; Humans; Hypothalamic Hormones; in vitro; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Migration; Neuropeptides; Phoenixin; Proliferation; SMIM20; GPR173; Migration; Endometriosis; Neuropeptides; Proliferation; Phoenixin; SMIM20
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2023.01.056

Endometriosis is one of the most common gynecologic diseases in women of reproductive age. The pathophysiology of endometriosis is still not fully understood. Phoenixin (PNX-14) is a newly discovered neuropeptide that regulates the hypothalamo–pituitary–gonadal (HPG) axis and reproductive functions. Recently, we reported that PNX-14, its precursor protein and receptor were expressed in human endometrium. Moreover, PNX-14 serum levels in endometriosis were reduced. This study aimed to evaluate the in vitro biological functions of physiological PNX-14 concentrations on the ectopic endometrium Z12 cells. The proliferation and migration of Z12 cells were assessed using the xCELLigence® RTCA DP system following 72 h of stimulation with 0.05 and 0.2 nM of PNX-14. GPR173 and small integral membrane protein 20 (SMIM20) gene expression was evaluated using quantitative polymerase chain reaction (qPCR) and the protein levels of GPR173 were analyzed using Western blot analysis. PNX-14 at the concentration observed in the serum of patients with endometriosis (0.05 nM) reduced GPR173 and increased SMIM20 expression, while protein levels of GPR173 remained unchanged. Cell proliferation was increased by the 0.02 nM PNX-14— the concentration found in healthy subjects. The 0.2 nM of PNX-14 decreased SMIM20 expression with no change to GPR173 expression and reduced ectopic epithelial cell proliferation during the first 5 h after stimulation. However, at 72 h, the proliferation increased. This study shows that PNX-14 at endometriosis specific concentration desensitized ectopic epithelium to PNX-14, and increased the expression of SMIM20 to restore the physiological levels of PNX-14. •Phenixin-14 at endometriosis-specific concentration increases Z12 cells migration.•Phenixin-14 at endometriosis-specific concentration decreases GPR173 expression.•Phenixin-14 at endometriosis-specific concentration increases SMIM20 expression.•Phenixin-14 at healthy women-specific concentration increases Z12 proliferation.•Phenixin-14 at healthy women-specific concentration decreases SMIM20 expression.