{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:33:04Z","timestamp":1773289984632,"version":"3.50.1"},"reference-count":45,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The development of white adipose tissue involves both the hypertrophy of existing adipocytes and the proliferation and differentiation of preadipocytes. Adipogenic differentiation is inhibited by TGF\u03b2 signaling through Smad2\/3, and IGF binding protein-3 (IGFBP-3) is also known to activate Smad2\/3 signaling in some cell types. We previously reported that exogenous or overexpressed IGFBP-3 inhibits adipogenesis in 3T3-L1 cells, but the role of endogenous IGFBP-3 in this process, and its possible interaction with TGF\u03b2, is not known. During 10-d adipogenic differentiation initiated by insulin, dexamethasone, and 3-isobutyl-1-methylxanthine, 3T3-L1 cells expressed increasing levels of IGFBP-3 and TGF\u03b21, secreting over 1000 pg\/ml of both proteins. Exogenous recombinant human IGFBP-3 paralleled TGF\u03b21 in stimulating Smad2 phosphorylation in 3T3-L1 preadipocytes, but no additive effect was observed for the two agents. In contrast, knockdown of endogenous IGFBP-3 by small interfering RNA (siRNA) significantly impaired Smad2 activation by 0.25 ng\/ml TGF\u03b21. Transient expression of human IGFBP-3 significantly inhibited the induction of adipogenic markers adiponectin and resistin, and the appearance of lipid droplets, but down-regulation of endogenous IGFBP-3 by siRNA had little effect on the expression of either marker during the 10-d differentiation, compared with nonsilencing control siRNA. However, down-regulation of endogenous IGFBP-3 using two different siRNA significantly reversed the inhibitory effect of TGF\u03b21 on both adiponectin and resistin induction. We conclude that IGFBP-3 activates inhibitory Smad signaling in 3T3-L1 cells and that endogenous IGFBP-3 modulates their adipogenic differentiation by regulating cell sensitivity towards the inhibitory effect of TGF\u03b2.<\/jats:p>","DOI":"10.1210\/en.2011-1444","type":"journal-article","created":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T17:45:03Z","timestamp":1348249503000},"page":"4799-4807","source":"Crossref","is-referenced-by-count":20,"title":["Interaction Between IGF Binding Protein-3 and TGF\u03b2 in the Regulation of Adipocyte Differentiation"],"prefix":"10.1210","volume":"153","author":[{"given":"Hasanthi C.","family":"de Silva","sequence":"first","affiliation":[{"name":"Kolling Institute of Medical Research, Royal North Shore Hospital (H.d.S., S.M.F., R.C.B.), Sydney, New South Wales 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sue M.","family":"Firth","sequence":"first","affiliation":[{"name":"Kolling Institute of Medical Research, Royal North Shore Hospital (H.d.S., S.M.F., R.C.B.), Sydney, New South Wales 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M.","family":"Twigg","sequence":"first","affiliation":[{"name":"Sydney Medical School (S.M.T.), University of Sydney, Sydney, New South Wales 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C.","family":"Baxter","sequence":"first","affiliation":[{"name":"Kolling Institute of Medical Research, Royal North Shore Hospital (H.d.S., S.M.F., R.C.B.), Sydney, New South Wales 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071612531284600_B1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1046\/j.1467-789X.2001.00042.x","article-title":"The biology of white adipocyte proliferation.","volume":"2","author":"Hausman","year":"2001","journal-title":"Obes 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