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

Kulinska, Karolina Iwona ; Bialas, Piotr LU orcid ; Dera-Szymanowska, Anna ; Billert, Maria ; Kotwicka, Małgorzata ; Szymanowski, Krzysztof and Wołun-Cholewa, Maria (2023) In Biochemical and Biophysical Research Communications 646. p.44-49
Abstract
Aim
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.

Methods
The proliferation and migration of Z12 cells were assessed using the xCELLigence® RTCA DP system following 72 h... (More)
Aim
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.

Methods
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.

Results
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.

Conclusions
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. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
in vitro, Migration, Proliferation, Endometrios, Phoenixin
in
Biochemical and Biophysical Research Communications
volume
646
pages
44 - 49
publisher
Elsevier
external identifiers
  • pmid:36706704
  • scopus:85146641249
ISSN
1090-2104
DOI
10.1016/j.bbrc.2023.01.056
language
English
LU publication?
yes
id
7eb12ecb-5159-4756-8e76-4aca1e8319c3
date added to LUP
2023-02-03 09:50:29
date last changed
2023-02-04 04:02:04
@article{7eb12ecb-5159-4756-8e76-4aca1e8319c3,
  abstract     = {{Aim<br/>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.<br/><br/>Methods<br/>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.<br/><br/>Results<br/>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.<br/><br/>Conclusions<br/>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.}},
  author       = {{Kulinska, Karolina Iwona and Bialas, Piotr and Dera-Szymanowska, Anna and Billert, Maria and Kotwicka, Małgorzata and Szymanowski, Krzysztof and Wołun-Cholewa, Maria}},
  issn         = {{1090-2104}},
  keywords     = {{in vitro; Migration; Proliferation; Endometrios; Phoenixin}},
  language     = {{eng}},
  month        = {{01}},
  pages        = {{44--49}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical and Biophysical Research Communications}},
  title        = {{The role of phoenixin in the proliferation and migration of ectopic epithelial cells in vitro}},
  url          = {{http://dx.doi.org/10.1016/j.bbrc.2023.01.056}},
  doi          = {{10.1016/j.bbrc.2023.01.056}},
  volume       = {{646}},
  year         = {{2023}},
}