{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:58:35Z","timestamp":1790315915150,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81171680"],"award-info":[{"award-number":["81171680"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>Elevated levels of follistatin\u2010like protein 1 (FSTL1) have been found both in mouse models for human rheumatoid arthritis (RA) and collagen\u2010induced arthritis (CIA). In this study, we elucidated the potential mechanisms by which FSTL1 contributes to the pathogenesis of RA. Fibroblast\u2010like synoviocytes (FLSs) were established from synovial tissues of RA patients and stimulated with human recombinant FSTL1. Protein and mRNA expression levels of select matrix metalloproteinases (i.e., MMP1, MMP3, MMP13) in FLS were measured by, respectively, real\u2010time RT\u2010qPCR and ELISA. Activation of MAPK and other pathways that affect MMPs were evaluated by Western blotting. We also compared concentrations of MMPs in plasma in RA patients versus healthy controls (HC). Expression levels of MMP1, MMP3, and MMP13 were clearly stimulated by FSTL1 in vitro. FSTL1 activated the inflammation\u2010related NF\u2010\u03baB signaling pathway, as well as all three mitogen\u2010activated protein kinase (MAPK) pathways and the JAK\/STAT3 pathway. Moreover, select chemical inhibitors that target p38 (SB203580), Erk1\/2 (SP600125), JNK (SCH772984), STAT3 (AG490), and NF\u2010\u03baB (BAY 11\u20137082) significantly attenuated MMP expression. Inhibition of Toll\u2010like receptor 4 by compound TAK\u2010242 significantly abolished those effects of FSTL1. Importantly, elevated plasma concentrations of MMP3 were found to correlate with plasma FSTL1 levels in RA patients. These findings suggest that FSTL1 accelerates RA progression by activating MAPK, JAK\/STAT3, and NF\u2010\u03baB pathways to enhance secretion of different MMPs and this enhancement is via TLR4. Targeting FSTL1 may provide a promising pharmacological drug therapy to ameliorate RA symptoms and perhaps reverse disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.26580","type":"journal-article","created":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T07:33:05Z","timestamp":1529652785000},"page":"454-463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Follistatin\u2010like protein 1 induction of matrix metalloproteinase 1, 3 and 13 gene expression in rheumatoid arthritis synoviocytes requires MAPK, JAK\/STAT3 and NF\u2010\u03baB pathways"],"prefix":"10.1002","volume":"234","author":[{"given":"Su","family":"Ni","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Orthopedics The Affiliated Changzhou No.2 People's Hospital With Nanjing Medical University Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenkai","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Orthopedics The Affiliated Changzhou No.2 People's Hospital With Nanjing Medical University Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanwei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Affiliated Changzhou No.2 People's Hospital With Nanjing Medical University Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology The First People's Hospital of Changzhou Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Wuhan Puai Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Orthopedics The Affiliated Changzhou No.2 People's Hospital With Nanjing Medical University Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Orthopedics The Affiliated Changzhou No.2 People's Hospital With Nanjing Medical University Changzhou China"},{"name":"Department of Orthopedics The Affiliated Changzhou No.2 People's Hospital With Nanjing Medical University Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4458-0946","authenticated-orcid":false,"given":"Andre J.","family":"van Wijnen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery and Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,22]]},"reference":[{"issue":"1","key":"e_1_2_8_2_1","first-page":"20","article-title":"The role of the synovial fibroblast in rheumatoid arthritis: Cartilage destruction and the regulation of matrix metalloproteinases","volume":"64","author":"Abeles A. 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