{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:05:20Z","timestamp":1790305520178,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2020R1F1A1060926"],"award-info":[{"award-number":["NRF-2020R1F1A1060926"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2022R1A2C1003782"],"award-info":[{"award-number":["NRF-2022R1A2C1003782"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chungnam National University Hospital Research Fund","award":["NRF-2020R1F1A1060926"],"award-info":[{"award-number":["NRF-2020R1F1A1060926"]}]},{"name":"Chungnam National University Hospital Research Fund","award":["NRF-2022R1A2C1003782"],"award-info":[{"award-number":["NRF-2022R1A2C1003782"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) patients have increased reactive oxygen species (ROS) levels and an impaired redox balance compared with FLS from control patients. Liver kinase B1 (LKB1) plays a key role in ROS scavenging and cellular metabolism in various cancers. Here, we aimed to determine the specific mechanism of LKB1 in RA pathogenesis. FLS were obtained from RA patients (n = 10). siRNA-induced LKB1 deficiency in RA FLS increased ROS levels via NADPH oxidase 4 (NOX4) upregulation. RA FLS migration and expression of inflammatory factors, including interleukin (IL)-1\u03b2, IL-6, IL-8, tumor necrosis factor-alpha (TNF-\u03b1), and vascular endothelial growth factor (VEGF), were enhanced by LKB1 deficiency. LKB1-deficient RA FLS showed increased sensitivity to oxidative stress damage caused by hydrogen peroxidase exposure. siRNA-induced solute carrier family 7 member 11 (SLC7A11) deficiency in RA FLS enhanced NOX4 and ROS expression and increased cell migration. When LKB1-deficient RA FLS were stimulated with an AMP-activated protein kinase (AMPK) activator, the LKB1-inhibition-induced cell migration significantly decreased through the restoration of SLC7A11\/NOX4 expression. LKB1 regulates the AMPK-mediated SLC7A11-NOX4-ROS pathway to control cell migration and inflammation. Our data indicate that LKB1 is a key regulator of redox homeostasis in RA FLS.<\/jats:p>","DOI":"10.3390\/cells12091263","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T01:28:28Z","timestamp":1682558908000},"page":"1263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["LKB1 Regulates Inflammation of Fibroblast-like Synoviocytes from Patients with Rheumatoid Arthritis via AMPK-Dependent SLC7A11-NOX4-ROS Signaling"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-4372","authenticated-orcid":false,"given":"Ha-Reum","family":"Lee","sequence":"first","affiliation":[{"name":"Research Institute for Medical Sciences, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4620-8803","authenticated-orcid":false,"given":"Su-Jin","family":"Yoo","sequence":"additional","affiliation":[{"name":"Research Institute for Medical Sciences, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Institute for Medical Sciences, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0076-0822","authenticated-orcid":false,"given":"Seong Wook","family":"Kang","sequence":"additional","affiliation":[{"name":"Research Institute for Medical Sciences, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/art.1780310302","article-title":"The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis","volume":"31","author":"Arnett","year":"1988","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0140-6736(09)60008-8","article-title":"Rheumatoid arthritis","volume":"373","author":"Klareskog","year":"2009","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.0105-2896.2009.00859.x","article-title":"Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis","volume":"233","author":"Bartok","year":"2010","journal-title":"Immunol. 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