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Recent studies have suggested that autophagy is involved in trophoblast invasion and may be associated with defective placentation underlying preeclampsia. We thus aimed to understand the mechanistic link between autophagy and trophoblast invasion. Using the two most commonly used trophoblast cell lines, JEG-3 and HTR-8\/SVneo, we inhibited autophagy by ATG5 and beclin-1 shRNA. Conversion of LC3-II was evaluated in ATG5 and beclin-1 knock-down cells in the presence of the lysosomal protease inhibitors E-64d and pepstatin A, to detect the efficiency of autophagy inhibition. Upon autophagy inhibition, we measured cell invasion, activity of NF-\u03baB and related signaling pathways, MMP-2, MMP-9, sFlt-1, and TNF-\u03b1 levels. Autophagy inhibition increased the invasiveness of these trophoblastic cell lines and increased Akt and NF-\u03baB activity as well as p65 expression. Of note, an NF-\u03baB inhibitor significantly attenuated the trophoblast invasion induced by autophagy inhibition. Autophagy inhibition was also associated with increased MMP-2 and MMP-9 levels and decreased the production of sFlt-1 and TNF-\u03b1. Collectively, our results indicate that autophagy regulates trophoblast invasiveness in which the NF-\u03baB pathway and MMP-2, MMP-9, sFlt-1 and TNF-\u03b1 levels are affected.<\/jats:p>","DOI":"10.1038\/s41598-020-70959-2","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T10:07:20Z","timestamp":1597918040000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Autophagy regulates trophoblast invasion by targeting NF-\u03baB activity"],"prefix":"10.1038","volume":"10","author":[{"given":"Soo-young","family":"Oh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2319-5878","authenticated-orcid":false,"given":"Jae Ryoung","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minji","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoo-Min","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Sun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon-Lim","family":"Suh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk-Joo","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheong-Rae","family":"Roh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"70959_CR1","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1126\/science.1111726","volume":"308","author":"CW Redman","year":"2005","unstructured":"Redman, C. 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