Modulation of matrix metalloproteases by ciliary neurotrophic factor in human placental development
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Published:2022-07-07
Issue:1
Volume:390
Page:113-129
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ISSN:0302-766X
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Container-title:Cell and Tissue Research
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language:en
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Short-container-title:Cell Tissue Res
Author:
Tossetta Giovanni, Fantone Sonia, Busilacchi Elena Marinelli, Di Simone NicolettaORCID, Giannubilo Stefano R., Scambia Giovanni, Giordano Antonio, Marzioni DanielaORCID
Abstract
AbstractCiliary neurotrophic factor (CNTF) is a pleiotropic cytokine that signals through a receptor complex containing a specific subunit, CNTF receptor α (CNTFRα). The two molecules are constitutively expressed in key structures for human placental growth and differentiation. The possible role of CNTF in enhancing cell proliferation and/or invasion during placental development and remodelling was investigated using HTR-8/SVneo and BeWo cells, taken respectively as cytotrophoblast and syncytiotrophoblast models. In both cell lines, treatment with human recombinant (hr) CNTF activated JAK2/STAT3 signalling and inhibited the ERK pathway. Interestingly, in HTR-8/SVneo cells, 50 ng hrCNTF induced significant downregulation of matrix metalloprotease (MMP)-1 and significant upregulation of MMP-9. Moreover, pharmacological inhibition of JAK2/STAT3 signalling by AG490 and curcumin resulted in MMP-9 downregulation; it activated the ERK signalling pathway and upregulated MMP-1 expression. Collectively, these data suggest a role for CNTF signalling in extravillous cytotrophoblast invasion through the modulation of specific MMPs.
Funder
Italian Ministry of Health Università Politecnica delle Marche
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Histology,Pathology and Forensic Medicine
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