Activin A Modulates Betaglycan Shedding via the ALK4-SMAD3-Dependent Pathway in Endometriotic Cells.
MMPs
SMAD2/3
activin A
betaglycan
endometriosis
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
24 11 2022
24 11 2022
Historique:
received:
01
08
2022
revised:
10
11
2022
accepted:
19
11
2022
entrez:
23
12
2022
pubmed:
24
12
2022
medline:
27
12
2022
Statut:
epublish
Résumé
The TGF-β superfamily members, activins and inhibins, are mainly involved in cell proliferation, cell survival, invasion, immune surveillance, and lesion growth in endometriosis. Herein, we investigated the modulation of the TGF-β type III receptor (betaglycan or BG) by activin A and inhibin A in endometriosis in vitro. Often, BG undergoes ectodomain shedding releasing soluble BG (sBG) which frequently antagonizes TGF-β signaling. The effects of activin A on BG shedding and signaling pathways involved were evaluated with the inhibitors LY364947 and SIS3, siRNA knockdown in human endometrial cells (12Z, THESC, Ishikawa, and primary stromal cells) and were quantified with BG ELISAs. The effects of activin A and inhibin A on the secretion of MMP2 and MMP3 were analyzed using ELISAs. The effects of activin A on the BG expression were analyzed using RT-qPCR and western blot. The CCK-8 and BrdU assays were used to evaluate the effects of the recombinant BG on cell viability and proliferation. Activin A stimulation resulted in a significant time- and dose-dependent reduction in BG shedding, which was found to be activin A/ALK-4/SMAD3- but not SMAD2-dependent. Activin A increased the BG mRNA expression but had no effect on the protein expression. Likewise, inhibin A was found to block BG shedding. Activin A, but not inhibin A, significantly enhanced the secretion of MMP2 and MMP3. The recombinant BG had no effect on the viability and proliferation of endometriotic cells. Together, these observations support a novel role for activin A with BG in modulating the TGF-β superfamily ligands in endometrial cells in vitro.
Identifiants
pubmed: 36551177
pii: biom12121749
doi: 10.3390/biom12121749
pmc: PMC9776114
pii:
doi:
Substances chimiques
activin A
0
Activins
104625-48-1
betaglycan
145170-29-2
Matrix Metalloproteinase 2
EC 3.4.24.24
Matrix Metalloproteinase 3
EC 3.4.24.17
Smad3 Protein
0
SMAD3 protein, human
0
Transforming Growth Factor beta
0
Receptors, Transforming Growth Factor beta
0
ACVR1B protein, human
EC 2.7.11.30
Activin Receptors, Type I
EC 2.7.11.30
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : German Academic Exchange Service
ID : 91560545
Organisme : German Academic Exchange Service
ID : 91731459
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Mol Med Rep. 2019 Jun;19(6):5053-5062
pubmed: 31059090
Nature. 2000 Mar 23;404(6776):411-4
pubmed: 10746731
J Immunol. 2000 Sep 15;165(6):2997-3003
pubmed: 10975808
Sci Signal. 2019 Feb 26;12(570):
pubmed: 30808818
Mol Endocrinol. 2009 Apr;23(4):539-48
pubmed: 19164448
J Reprod Dev. 2016 Apr 22;62(2):213-8
pubmed: 26853786
J Reprod Fertil. 1988 May;83(1):239-48
pubmed: 3165129
Biology (Basel). 2022 Mar 26;11(4):
pubmed: 35453712
Carcinogenesis. 2008 Mar;29(3):528-35
pubmed: 18174241
Biol Reprod. 2012 Dec 13;87(6):135
pubmed: 23077171
Nat Rev Dis Primers. 2018 Jul 19;4(1):9
pubmed: 30026507
J Cell Biol. 1989 Dec;109(6 Pt 1):3137-45
pubmed: 2592419
Endocrinology. 2009 Apr;150(4):1904-11
pubmed: 19022896
Am J Pathol. 2001 Nov;159(5):1839-52
pubmed: 11696444
Mol Cell Endocrinol. 2009 Aug 13;307(1-2):149-56
pubmed: 19524135
BJOG. 2008 Oct;115(11):1382-91
pubmed: 18715240
Hum Reprod. 2010 Jan;25(1):101-9
pubmed: 19892717
J Cell Biol. 1994 Feb;124(4):557-68
pubmed: 8106553
Mol Endocrinol. 2002 Dec;16(12):2754-63
pubmed: 12456797
Aust N Z J Obstet Gynaecol. 2006 Apr;46(2):148-53
pubmed: 16638039
Cytokine. 2020 Sep;133:155105
pubmed: 32438278
Hum Reprod. 2007 Aug;22(8):2120-7
pubmed: 17609243
Nat Rev Endocrinol. 2014 May;10(5):261-75
pubmed: 24366116
Fertil Steril. 2001 Feb;75(2):367-73
pubmed: 11172841
Am J Cancer Res. 2015 Apr 15;5(5):1706-17
pubmed: 26175939
Cell. 1991 Nov 15;67(4):797-805
pubmed: 1657407
Cancer Res. 2008 Sep 15;68(18):7304-12
pubmed: 18794117
Curr Opin Obstet Gynecol. 2003 Aug;15(4):321-6
pubmed: 12858105
Endocrinology. 2004 May;145(5):2291-6
pubmed: 14726435
Carcinogenesis. 2010 Feb;31(2):175-83
pubmed: 19955393
Immunol Cell Biol. 2001 Jun;79(3):291-7
pubmed: 11380683
J Transl Med. 2020 Dec 11;18(1):478
pubmed: 33308241
Fertil Steril. 2008 Oct;90(4):972-87
pubmed: 18001719
Gynecol Endocrinol. 2015 Jul;31(7):511-5
pubmed: 25986305
Oncogene. 2018 Apr;37(16):2197-2212
pubmed: 29391598
Nature. 1999 Sep 30;401(6752):480-5
pubmed: 10519551
Endocrinology. 1993 Jun;132(6):2732-4
pubmed: 7684983
J Minim Invasive Gynecol. 2020 Feb;27(2):452-461
pubmed: 31816389
Cancer Res. 2007 Feb 1;67(3):1090-8
pubmed: 17283142
Adv Wound Care (New Rochelle). 2013 Jun;2(5):195-214
pubmed: 24527343
Cell Signal. 2010 Aug;22(8):1163-74
pubmed: 20153821
Endocrinology. 2006 Feb;147(2):724-32
pubmed: 16282351
Hum Reprod Update. 2017 Sep 1;23(5):548-559
pubmed: 28903471
Int J Mol Med. 2010 Jan;25(1):17-23
pubmed: 19956897
Cold Spring Harb Perspect Biol. 2016 Jul 01;8(7):
pubmed: 27328872
Cell. 1993 Jul 2;73(7):1435-44
pubmed: 8391934
J Clin Endocrinol Metab. 2015 Nov;100(11):E1415-27
pubmed: 26305619
Mol Endocrinol. 2010 Mar;24(3):608-20
pubmed: 20160125
Mol Med Rep. 2018 Sep;18(3):3123-3136
pubmed: 30066912
Mol Cell Endocrinol. 2011 Jun 6;339(1-2):180-9
pubmed: 21550381
Int J Mol Sci. 2019 Dec 09;20(24):
pubmed: 31835434
Cell. 1991 Nov 15;67(4):785-95
pubmed: 1657406
Endocrinology. 2006 Jul;147(7):3462-71
pubmed: 16601134
J Biol Chem. 2004 Feb 27;279(9):7721-33
pubmed: 14672946
EMBO J. 2006 Mar 8;25(5):1035-45
pubmed: 16482217