{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:16:57Z","timestamp":1761707817497,"version":"build-2065373602"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2003,6,3]],"date-time":"2003-06-03T00:00:00Z","timestamp":1054598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA 38808"],"award-info":[{"award-number":["CA 38808"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001869","name":"Academia Sinica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2003,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The activity and plasma clearance of transforming growth factor (TGF)\u2010\u03b2 are known to be regulated by activated \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    \u2010macroglobulin (\u03b1\n                    <jats:sub>2<\/jats:sub>\n                    M*). This has been implicated in pathophysiological processes, but no small molecule compounds have been reported to modulate TGF\u2010\u03b2 activity by affecting the interaction of TGF\u2010\u03b2 and \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    M*. Here, we demonstrate that fatty acids are capable of inhibiting complex formation of TGF\u2010\u03b2 isoforms and \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    M* as demonstrated by nondenaturing and sodium dodecyl sulfate\u2010polyacrylamide gel electrophoresis. This is dependent on carbon chain length (C20, C18, C16, C14 &gt; C12 &gt; C10), degree of unsaturation (polyunsaturated &gt; saturated), and TGF\u2010\u03b2 isoforms (TGF\u2010\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    &gt; TGF\u2010\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    &gt; TGF\u2010\u03b2\n                    <jats:sub>3<\/jats:sub>\n                    ). Arachidonic acid, which is one of the most potent inhibitors, is also capable of dissociating TGF\u2010\u03b2\u2010\u03b1\n                    <jats:sub>2<\/jats:sub>\n                    M* complexes, but higher concentrations are required. Arachidonic acid appears to inhibit TGF\u2010\u03b2\u2010\u03b1\n                    <jats:sub>2<\/jats:sub>\n                    M* complex formation by binding specifically to \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    M* as demonstrated by gel filtration chromatography. Arachidonic acid reverses the inhibitory effect of \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    M* on TGF\u2010\u03b2 binding, TGF\u2010\u03b2\u2010induced growth inhibition, and TGF\u2010\u03b2\u2010induced transcriptional activation in mink lung epithelial cells and affects plasma clearance of TGF\u2010\u03b2\u2010\u03b1\n                    <jats:sub>2<\/jats:sub>\n                    M* complexes in mice. These results show that fatty acids are effective modulators of TGF\u2010\u03b2 activity and plasma clearance and may be useful in treating human diseases through their effects on the interaction of TGF\u2010\u03b2 and \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    M*.\n                  <\/jats:p>","DOI":"10.1096\/fj.02-1063fje","type":"journal-article","created":{"date-parts":[[2003,7,29]],"date-time":"2003-07-29T16:11:57Z","timestamp":1059495117000},"page":"1-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Fatty acids modulate transforming growth factor\u2010\u03b2 activity and plasma clearance"],"prefix":"10.1096","volume":"17","author":[{"given":"Thai-Yen","family":"Ling","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences Academia Sinica  Taipei Taiwan"}]},{"given":"Yen-Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Graduate Institute of Medical Sciences Taipei Medical University  Taipei Taiwan"}]},{"given":"Ming-Chih","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences Academia Sinica  Taipei Taiwan"}]},{"given":"Shuan Shian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Saint Louis University School of Medicine  St. Louis MO 63104"}]},{"given":"Jung San","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences Academia Sinica  Taipei Taiwan"},{"name":"Department of Biochemistry and Molecular Biology Saint Louis University School of Medicine  St. Louis MO 63104"}]}],"member":"311","published-online":{"date-parts":[[2003,6,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-49295-2_8"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.06.110190.003121"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000060162"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(96)00120-3"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041370120"},{"key":"e_1_2_6_7_1","first-page":"37","article-title":"Vascular cells respond differentially to transforming growth factors \u03b21 and \u03b22 in vitro","volume":"138","author":"Merwin J. 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