Estradiol modulates TGF-β1 expression and its signaling pathway in thyroid stromal cells
The higher prevalence of thyroid disease in women suggests that estrogen (E2) might be involved in the pathophysiology of thyroid dysfunction. To approach the question of the effect of stromal cells in the modulation of thyroid epithelial cells activity, we established and characterized a homogeneou...
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| creator | Gantus, M.A.V. Alves, L.M. Stipursky, J. Souza, E.C.L. Teodoro, A.J. Alves, T.R. Carvalho, D.P. Martinez, A.M.B. Gomes, F.C.A. Nasciutti, L.E. |
| description | The higher prevalence of thyroid disease in women suggests that estrogen (E2) might be involved in the pathophysiology of thyroid dysfunction. To approach the question of the effect of stromal cells in the modulation of thyroid epithelial cells activity, we established and characterized a homogeneous stromal cell population (TS7 cells) of rat thyroid gland. These fibroblastic cells synthesize the cytoskeleton proteins α-smooth muscle actin and vimentin, produce basement membrane components and express the cytokine transforming growth factor beta 1 (TGF-β1). Here, we hypothesized that the effects of E2 on follicular thyroid cells are mediated by TGF-β1 synthesis and secretion by stromal cells (paracrine action). Thus we investigated the effect of E2 on TGF-β1 synthesis and its signaling pathway in TS7 cells. In addition, we analyzed the role of TGF-β1 signaling pathway as mediator of TS7-PC CL3 thyroid epithelial cells interactions. We report that TS7 stromal cells expressed α and β estrogen receptors (ERα and ERβ). Further, both isoforms of TGF-β1 receptors, TGFRI and TGFRII, were also identified in TS7 cells, suggesting that these cells might be a target for this cytokine
in vitro. Treatment of TS7 cells with E2 induced both synthesis and secretion of TGF-β1. This event was followed by phosphorylation of the transcription factor Smad2, a hallmark of TGF-β1 pathway activation. Co-culture of PC CL3 cells onto TS7 cells monolayers yielded round aggregates of PC CL3 cells surrounded by TS7 cells. TS7 cells induced a decrease in iodide uptake by PC CL3 cells, probably by a mechanism involving TGF-β1. Moreover, E2 affected synthesis and organization of the extracellular matrix (ECM) components, tenascin C and chondroitin sulfate, in these co-culture cells. Our results point to the TGF-β1/Smad-2 signaling pathway as a putative target of estrogen actions on thyroid stromal cells and contribute to understanding the interplay between stromal and follicular cells in thyroid physiology. |
| doi_str_mv | 10.1016/j.mce.2011.02.001 |
| format | Article |
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in vitro. Treatment of TS7 cells with E2 induced both synthesis and secretion of TGF-β1. This event was followed by phosphorylation of the transcription factor Smad2, a hallmark of TGF-β1 pathway activation. Co-culture of PC CL3 cells onto TS7 cells monolayers yielded round aggregates of PC CL3 cells surrounded by TS7 cells. TS7 cells induced a decrease in iodide uptake by PC CL3 cells, probably by a mechanism involving TGF-β1. Moreover, E2 affected synthesis and organization of the extracellular matrix (ECM) components, tenascin C and chondroitin sulfate, in these co-culture cells. Our results point to the TGF-β1/Smad-2 signaling pathway as a putative target of estrogen actions on thyroid stromal cells and contribute to understanding the interplay between stromal and follicular cells in thyroid physiology.</description><identifier>ISSN: 0303-7207</identifier><identifier>EISSN: 1872-8057</identifier><identifier>DOI: 10.1016/j.mce.2011.02.001</identifier><identifier>PMID: 21315800</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>actin ; Animals ; basement membrane ; Cell Shape ; Cell Survival ; Cells, Cultured ; chondroitin sulfate ; coculture ; Coculture Techniques ; cytokines ; Cytoskeletal Proteins - metabolism ; cytoskeleton ; epithelial cells ; estradiol ; Estradiol - metabolism ; Estrogen ; Estrogen Receptor alpha - metabolism ; Estrogen Receptor beta - metabolism ; estrogen receptors ; Extracellular matrix ; Extracellular Matrix - metabolism ; Female ; iodides ; muscles ; pathophysiology ; PC CL3 cells ; phosphorylation ; Rats ; Rats, Wistar ; Receptors, Transforming Growth Factor beta - metabolism ; secretion ; Signal Transduction ; Smad Proteins - metabolism ; Stromal cells ; Stromal Cells - metabolism ; Stromal Cells - secretion ; TGF-β1 ; Thyroid ; thyroid gland ; Thyroid Gland - cytology ; Thyroid Gland - metabolism ; transcription factors ; Transcription, Genetic ; transforming growth factor beta 1 ; Transforming Growth Factor beta1 - genetics ; Transforming Growth Factor beta1 - metabolism ; vimentin ; women</subject><ispartof>Molecular and cellular endocrinology, 2011-04, Vol.337 (1), p.71-79</ispartof><rights>2011 Elsevier Ireland Ltd</rights><rights>Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c291t-90cf5722af1c065be194b9366a30fcc5bbd647ac0c3eeddead317856c45446c93</citedby><cites>FETCH-LOGICAL-c291t-90cf5722af1c065be194b9366a30fcc5bbd647ac0c3eeddead317856c45446c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mce.2011.02.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21315800$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gantus, M.A.V.</creatorcontrib><creatorcontrib>Alves, L.M.</creatorcontrib><creatorcontrib>Stipursky, J.</creatorcontrib><creatorcontrib>Souza, E.C.L.</creatorcontrib><creatorcontrib>Teodoro, A.J.</creatorcontrib><creatorcontrib>Alves, T.R.</creatorcontrib><creatorcontrib>Carvalho, D.P.</creatorcontrib><creatorcontrib>Martinez, A.M.B.</creatorcontrib><creatorcontrib>Gomes, F.C.A.</creatorcontrib><creatorcontrib>Nasciutti, L.E.</creatorcontrib><title>Estradiol modulates TGF-β1 expression and its signaling pathway in thyroid stromal cells</title><title>Molecular and cellular endocrinology</title><addtitle>Mol Cell Endocrinol</addtitle><description>The higher prevalence of thyroid disease in women suggests that estrogen (E2) might be involved in the pathophysiology of thyroid dysfunction. To approach the question of the effect of stromal cells in the modulation of thyroid epithelial cells activity, we established and characterized a homogeneous stromal cell population (TS7 cells) of rat thyroid gland. These fibroblastic cells synthesize the cytoskeleton proteins α-smooth muscle actin and vimentin, produce basement membrane components and express the cytokine transforming growth factor beta 1 (TGF-β1). Here, we hypothesized that the effects of E2 on follicular thyroid cells are mediated by TGF-β1 synthesis and secretion by stromal cells (paracrine action). Thus we investigated the effect of E2 on TGF-β1 synthesis and its signaling pathway in TS7 cells. In addition, we analyzed the role of TGF-β1 signaling pathway as mediator of TS7-PC CL3 thyroid epithelial cells interactions. We report that TS7 stromal cells expressed α and β estrogen receptors (ERα and ERβ). Further, both isoforms of TGF-β1 receptors, TGFRI and TGFRII, were also identified in TS7 cells, suggesting that these cells might be a target for this cytokine
in vitro. Treatment of TS7 cells with E2 induced both synthesis and secretion of TGF-β1. This event was followed by phosphorylation of the transcription factor Smad2, a hallmark of TGF-β1 pathway activation. Co-culture of PC CL3 cells onto TS7 cells monolayers yielded round aggregates of PC CL3 cells surrounded by TS7 cells. TS7 cells induced a decrease in iodide uptake by PC CL3 cells, probably by a mechanism involving TGF-β1. Moreover, E2 affected synthesis and organization of the extracellular matrix (ECM) components, tenascin C and chondroitin sulfate, in these co-culture cells. Our results point to the TGF-β1/Smad-2 signaling pathway as a putative target of estrogen actions on thyroid stromal cells and contribute to understanding the interplay between stromal and follicular cells in thyroid physiology.</description><subject>actin</subject><subject>Animals</subject><subject>basement membrane</subject><subject>Cell Shape</subject><subject>Cell Survival</subject><subject>Cells, Cultured</subject><subject>chondroitin sulfate</subject><subject>coculture</subject><subject>Coculture Techniques</subject><subject>cytokines</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>cytoskeleton</subject><subject>epithelial cells</subject><subject>estradiol</subject><subject>Estradiol - metabolism</subject><subject>Estrogen</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogen Receptor beta - metabolism</subject><subject>estrogen receptors</subject><subject>Extracellular matrix</subject><subject>Extracellular Matrix - metabolism</subject><subject>Female</subject><subject>iodides</subject><subject>muscles</subject><subject>pathophysiology</subject><subject>PC CL3 cells</subject><subject>phosphorylation</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Transforming Growth Factor beta - metabolism</subject><subject>secretion</subject><subject>Signal Transduction</subject><subject>Smad Proteins - metabolism</subject><subject>Stromal cells</subject><subject>Stromal Cells - metabolism</subject><subject>Stromal Cells - secretion</subject><subject>TGF-β1</subject><subject>Thyroid</subject><subject>thyroid gland</subject><subject>Thyroid Gland - cytology</subject><subject>Thyroid Gland - metabolism</subject><subject>transcription factors</subject><subject>Transcription, Genetic</subject><subject>transforming growth factor beta 1</subject><subject>Transforming Growth Factor beta1 - genetics</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>vimentin</subject><subject>women</subject><issn>0303-7207</issn><issn>1872-8057</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAURS0EokPhA9iAd6wSnu3YTsQKVW1BqsSi7aIry7Ffph4l8WBnCvNbfEi_qR5NYcnqbc49ejqEvGdQM2Dq86aeHNYcGKuB1wDsBVmxVvOqBalfkhUIEJXmoE_Im5w3AKAlb1-TE84Eky3Aityd5yVZH-JIp-h3o10w05vLi-rxD6P4e5sw5xBnamdPw5JpDuvZjmFe061d7n_ZPQ0zXe73KQZPiypOdqQOxzG_Ja8GO2Z893xPye3F-c3Zt-rqx-X3s69XleMdW6oO3CA153ZgDpTskXVN3wmlrIDBOdn3XjXaOnAC0Xu0XjDdSuUa2TTKdeKUfDp6tyn-3GFezBTy4QM7Y9xl0yrGoRMaCsmOpEsx54SD2aYw2bQ3DMwhqNmYEtQcghrgpgQtmw_P9l0_of-3-FuwAB-PwGCjsesUsrm9LgZZ1i2oRhXiy5HAUuEhYDLZBZwd-pDQLcbH8J8HngASyJCD</recordid><startdate>20110430</startdate><enddate>20110430</enddate><creator>Gantus, M.A.V.</creator><creator>Alves, L.M.</creator><creator>Stipursky, J.</creator><creator>Souza, E.C.L.</creator><creator>Teodoro, A.J.</creator><creator>Alves, T.R.</creator><creator>Carvalho, D.P.</creator><creator>Martinez, A.M.B.</creator><creator>Gomes, F.C.A.</creator><creator>Nasciutti, L.E.</creator><general>Elsevier Ireland Ltd</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20110430</creationdate><title>Estradiol modulates TGF-β1 expression and its signaling pathway in thyroid stromal cells</title><author>Gantus, M.A.V. ; Alves, L.M. ; Stipursky, J. ; Souza, E.C.L. ; Teodoro, A.J. ; Alves, T.R. ; Carvalho, D.P. ; Martinez, A.M.B. ; Gomes, F.C.A. ; Nasciutti, L.E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c291t-90cf5722af1c065be194b9366a30fcc5bbd647ac0c3eeddead317856c45446c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>actin</topic><topic>Animals</topic><topic>basement membrane</topic><topic>Cell Shape</topic><topic>Cell Survival</topic><topic>Cells, Cultured</topic><topic>chondroitin sulfate</topic><topic>coculture</topic><topic>Coculture Techniques</topic><topic>cytokines</topic><topic>Cytoskeletal Proteins - metabolism</topic><topic>cytoskeleton</topic><topic>epithelial cells</topic><topic>estradiol</topic><topic>Estradiol - metabolism</topic><topic>Estrogen</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Estrogen Receptor beta - metabolism</topic><topic>estrogen receptors</topic><topic>Extracellular matrix</topic><topic>Extracellular Matrix - metabolism</topic><topic>Female</topic><topic>iodides</topic><topic>muscles</topic><topic>pathophysiology</topic><topic>PC CL3 cells</topic><topic>phosphorylation</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Transforming Growth Factor beta - metabolism</topic><topic>secretion</topic><topic>Signal Transduction</topic><topic>Smad Proteins - metabolism</topic><topic>Stromal cells</topic><topic>Stromal Cells - metabolism</topic><topic>Stromal Cells - secretion</topic><topic>TGF-β1</topic><topic>Thyroid</topic><topic>thyroid gland</topic><topic>Thyroid Gland - cytology</topic><topic>Thyroid Gland - metabolism</topic><topic>transcription factors</topic><topic>Transcription, Genetic</topic><topic>transforming growth factor beta 1</topic><topic>Transforming Growth Factor beta1 - genetics</topic><topic>Transforming Growth Factor beta1 - metabolism</topic><topic>vimentin</topic><topic>women</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gantus, M.A.V.</creatorcontrib><creatorcontrib>Alves, L.M.</creatorcontrib><creatorcontrib>Stipursky, J.</creatorcontrib><creatorcontrib>Souza, E.C.L.</creatorcontrib><creatorcontrib>Teodoro, A.J.</creatorcontrib><creatorcontrib>Alves, T.R.</creatorcontrib><creatorcontrib>Carvalho, D.P.</creatorcontrib><creatorcontrib>Martinez, A.M.B.</creatorcontrib><creatorcontrib>Gomes, F.C.A.</creatorcontrib><creatorcontrib>Nasciutti, L.E.</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gantus, M.A.V.</au><au>Alves, L.M.</au><au>Stipursky, J.</au><au>Souza, E.C.L.</au><au>Teodoro, A.J.</au><au>Alves, T.R.</au><au>Carvalho, D.P.</au><au>Martinez, A.M.B.</au><au>Gomes, F.C.A.</au><au>Nasciutti, L.E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estradiol modulates TGF-β1 expression and its signaling pathway in thyroid stromal cells</atitle><jtitle>Molecular and cellular endocrinology</jtitle><addtitle>Mol Cell Endocrinol</addtitle><date>2011-04-30</date><risdate>2011</risdate><volume>337</volume><issue>1</issue><spage>71</spage><epage>79</epage><pages>71-79</pages><issn>0303-7207</issn><eissn>1872-8057</eissn><abstract>The higher prevalence of thyroid disease in women suggests that estrogen (E2) might be involved in the pathophysiology of thyroid dysfunction. To approach the question of the effect of stromal cells in the modulation of thyroid epithelial cells activity, we established and characterized a homogeneous stromal cell population (TS7 cells) of rat thyroid gland. These fibroblastic cells synthesize the cytoskeleton proteins α-smooth muscle actin and vimentin, produce basement membrane components and express the cytokine transforming growth factor beta 1 (TGF-β1). Here, we hypothesized that the effects of E2 on follicular thyroid cells are mediated by TGF-β1 synthesis and secretion by stromal cells (paracrine action). Thus we investigated the effect of E2 on TGF-β1 synthesis and its signaling pathway in TS7 cells. In addition, we analyzed the role of TGF-β1 signaling pathway as mediator of TS7-PC CL3 thyroid epithelial cells interactions. We report that TS7 stromal cells expressed α and β estrogen receptors (ERα and ERβ). Further, both isoforms of TGF-β1 receptors, TGFRI and TGFRII, were also identified in TS7 cells, suggesting that these cells might be a target for this cytokine
in vitro. Treatment of TS7 cells with E2 induced both synthesis and secretion of TGF-β1. This event was followed by phosphorylation of the transcription factor Smad2, a hallmark of TGF-β1 pathway activation. Co-culture of PC CL3 cells onto TS7 cells monolayers yielded round aggregates of PC CL3 cells surrounded by TS7 cells. TS7 cells induced a decrease in iodide uptake by PC CL3 cells, probably by a mechanism involving TGF-β1. Moreover, E2 affected synthesis and organization of the extracellular matrix (ECM) components, tenascin C and chondroitin sulfate, in these co-culture cells. Our results point to the TGF-β1/Smad-2 signaling pathway as a putative target of estrogen actions on thyroid stromal cells and contribute to understanding the interplay between stromal and follicular cells in thyroid physiology.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>21315800</pmid><doi>10.1016/j.mce.2011.02.001</doi><tpages>9</tpages></addata></record> |
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| subjects | actin Animals basement membrane Cell Shape Cell Survival Cells, Cultured chondroitin sulfate coculture Coculture Techniques cytokines Cytoskeletal Proteins - metabolism cytoskeleton epithelial cells estradiol Estradiol - metabolism Estrogen Estrogen Receptor alpha - metabolism Estrogen Receptor beta - metabolism estrogen receptors Extracellular matrix Extracellular Matrix - metabolism Female iodides muscles pathophysiology PC CL3 cells phosphorylation Rats Rats, Wistar Receptors, Transforming Growth Factor beta - metabolism secretion Signal Transduction Smad Proteins - metabolism Stromal cells Stromal Cells - metabolism Stromal Cells - secretion TGF-β1 Thyroid thyroid gland Thyroid Gland - cytology Thyroid Gland - metabolism transcription factors Transcription, Genetic transforming growth factor beta 1 Transforming Growth Factor beta1 - genetics Transforming Growth Factor beta1 - metabolism vimentin women |
| title | Estradiol modulates TGF-β1 expression and its signaling pathway in thyroid stromal cells |
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