{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:55:13Z","timestamp":1790142913840,"version":"4.0.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1-2","license":[{"start":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T00:00:00Z","timestamp":1414540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cell Biochem"],"published-print":{"date-parts":[[2015,2]]},"DOI":"10.1007\/s11010-014-2258-1","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T12:05:25Z","timestamp":1414497925000},"page":"17-28","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Smad2 protects against TGF-\u03b21\/Smad3-mediated collagen synthesis in human hepatic stellate cells during hepatic fibrosis"],"prefix":"10.1007","volume":"400","author":[{"given":"Lei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-ming","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,10,29]]},"reference":[{"key":"2258_CR1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1089\/wound.2013.0429","volume":"2","author":"KW Finnson","year":"2013","unstructured":"Finnson KW, McLean S, Di Guglielmo GM, Philip A (2013) Dynamics of transforming growth factor beta signaling in wound healing and scarring. Adv Wound Care (New Rochelle) 2:195\u2013214","journal-title":"Adv Wound Care (New Rochelle)"},{"key":"2258_CR2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1089\/wound.2012.0406","volume":"2","author":"M Pakyari","year":"2013","unstructured":"Pakyari M, Farrokhi A, Maharlooei MK, Ghahary A (2013) Critical role of transforming growth factor beta in different phases of wound healing. Adv Wound Care (New Rochelle) 2:215\u2013224","journal-title":"Adv Wound Care (New Rochelle)"},{"key":"2258_CR3","doi-asserted-by":"crossref","first-page":"G845","DOI":"10.1152\/ajpgi.2000.279.5.G845","volume":"279","author":"RG Wells","year":"2000","unstructured":"Wells RG (2000) Fibrogenesis. V. TGF-beta signaling pathways. Am J Physiol Gastrointest Liver Physiol 279:G845\u2013G850","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2258_CR4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00441-011-1201-y","volume":"347","author":"Y Mu","year":"2012","unstructured":"Mu Y, Gudey SK, Landstrom M (2012) Non-Smad signaling pathways. Cell Tissue Res 347:11\u201320","journal-title":"Cell Tissue Res"},{"key":"2258_CR5","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/labinvest.2014.43","volume":"94","author":"J Chen","year":"2014","unstructured":"Chen J, Xia Y, Lin X, Feng XH, Wang Y (2014) Smad3 signaling activates bone marrow-derived fibroblasts in renal fibrosis. Lab Invest 94:545\u2013556","journal-title":"Lab Invest"},{"key":"2258_CR6","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.cytogfr.2013.06.002","volume":"24","author":"K Matsuzaki","year":"2013","unstructured":"Matsuzaki K (2013) Smad phospho-isoforms direct context-dependent TGF-beta signaling. Cytokine Growth Factor Rev 24:385\u2013399","journal-title":"Cytokine Growth Factor Rev"},{"key":"2258_CR7","doi-asserted-by":"crossref","first-page":"6748","DOI":"10.1038\/sj.onc.1206791","volume":"22","author":"A Kretschmer","year":"2003","unstructured":"Kretschmer A, Moepert K, Dames S, Sternberger M, Kaufmann J, Klippel A (2003) Differential regulation of TGF-beta signaling through Smad2, Smad3 and Smad4. Oncogene 22:6748\u20136763","journal-title":"Oncogene"},{"key":"2258_CR8","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1074\/jbc.274.2.703","volume":"274","author":"K Yagi","year":"1999","unstructured":"Yagi K, Goto D, Hamamoto T, Takenoshita S, Kato M, Miyazono K (1999) Alternatively spliced variant of Smad2 lacking exon 3. Comparison with wild-type Smad2 and Smad3. J Biol Chem 274:703\u2013709","journal-title":"J Biol Chem"},{"key":"2258_CR9","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/31693","volume":"393","author":"M Nomura","year":"1998","unstructured":"Nomura M, Li E (1998) Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature 393:786\u2013790","journal-title":"Nature"},{"key":"2258_CR10","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1093\/emboj\/18.5.1280","volume":"18","author":"X Yang","year":"1999","unstructured":"Yang X, Letterio JJ, Lechleider RJ, Chen L, Hayman R, Gu H, Roberts AB, Deng C (1999) Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta. EMBO J 18:1280\u20131291","journal-title":"EMBO J"},{"key":"2258_CR11","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nature02006","volume":"425","author":"R Derynck","year":"2003","unstructured":"Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425:577\u2013584","journal-title":"Nature"},{"key":"2258_CR12","doi-asserted-by":"crossref","first-page":"12595","DOI":"10.1073\/pnas.96.22.12595","volume":"96","author":"J Heyer","year":"1999","unstructured":"Heyer J, Escalante-Alcalde D, Lia M, Boettinger E, Edelmann W, Stewart CL, Kucherlapati R (1999) Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis. Proc Natl Acad Sci USA 96:12595\u201312600","journal-title":"Proc Natl Acad Sci USA"},{"key":"2258_CR13","doi-asserted-by":"crossref","first-page":"9378","DOI":"10.1073\/pnas.95.16.9378","volume":"95","author":"M Weinstein","year":"1998","unstructured":"Weinstein M, Yang X, Li C, Xu X, Gotay J, Deng CX (1998) Failure of egg cylinder elongation and mesoderm induction in mouse embryos lacking the tumor suppressor smad2. Proc Natl Acad Sci U S A 95:9378\u20139383","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2258_CR14","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1128\/MCB.19.4.2495","volume":"19","author":"MB Datto","year":"1999","unstructured":"Datto MB, Frederick JP, Pan L, Borton AJ, Zhuang Y, Wang XF (1999) Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction. Mol Cell Biol 19:2495\u20132504","journal-title":"Mol Cell Biol"},{"key":"2258_CR15","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/sj.emboj.7600069","volume":"23","author":"J Zavadil","year":"2004","unstructured":"Zavadil J, Cermak L, Soto-Nieves N, Bottinger EP (2004) Integration of TGF-beta\/Smad and Jagged1\/Notch signalling in epithelial-to-mesenchymal transition. EMBO J 23:1155\u20131165","journal-title":"EMBO J"},{"key":"2258_CR16","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cytogfr.2005.09.008","volume":"17","author":"AB Roberts","year":"2006","unstructured":"Roberts AB, Tian F, Byfield SD, Stuelten C, Ooshima A, Saika S, Flanders KC (2006) Smad3 is key to TGF-beta-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis. Cytokine Growth Factor Rev 17:19\u201327","journal-title":"Cytokine Growth Factor Rev"},{"key":"2258_CR17","doi-asserted-by":"crossref","first-page":"14769","DOI":"10.1073\/pnas.95.25.14769","volume":"95","author":"L Vindevoghel","year":"1998","unstructured":"Vindevoghel L, Lechleider RJ, Kon A, De Caestecker MP, Uitto J, Roberts AB, Mauviel A (1998) SMAD3\/4-dependent transcriptional activation of the human type VII collagen gene (COL7A1) promoter by transforming growth factor beta. Proc Natl Acad Sci U S A 95:14769\u201314774","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2258_CR18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1046\/j.1523-1747.1999.00477.x","volume":"112","author":"SJ Chen","year":"1999","unstructured":"Chen SJ, Yuan W, Mori Y, Levenson A, Trojanowska M, Varga J (1999) Stimulation of type I collagen transcription in human skin fibroblasts by TGF-beta: involvement of Smad 3. J Invest Dermatol 112:49\u201357","journal-title":"J Invest Dermatol"},{"key":"2258_CR19","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1053\/jhep.2003.50196","volume":"37","author":"E Ueberham","year":"2003","unstructured":"Ueberham E, Low R, Ueberham U, Schonig K, Bujard H, Gebhardt R (2003) Conditional tetracycline-regulated expression of TGF-beta1 in liver of transgenic mice leads to reversible intermediary fibrosis. Hepatology 37:1067\u20131078","journal-title":"Hepatology"},{"key":"2258_CR20","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1177\/030089161009600503","volume":"96","author":"E Su","year":"2010","unstructured":"Su E, Han X, Jiang G (2010) The transforming growth factor beta 1\/SMAD signaling pathway involved in human chronic myeloid leukemia. Tumori 96:659\u2013666","journal-title":"Tumori"},{"key":"2258_CR21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.tibs.2004.03.008","volume":"29","author":"P Dijke ten","year":"2004","unstructured":"ten Dijke P, Hill CS (2004) New insights into TGF-beta-Smad signalling. Trends Biochem Sci 29:265\u2013273","journal-title":"Trends Biochem Sci"},{"key":"2258_CR22","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.1091\/mbc.E05-02-0149","volume":"16","author":"M Uemura","year":"2005","unstructured":"Uemura M, Swenson ES, Gaca MD, Giordano FJ, Reiss M, Wells RG (2005) Smad2 and Smad3 play different roles in rat hepatic stellate cell function and alpha-smooth muscle actin organization. Mol Biol Cell 16:4214\u20134224","journal-title":"Mol Biol Cell"},{"key":"2258_CR23","doi-asserted-by":"crossref","first-page":"11721","DOI":"10.1074\/jbc.M207728200","volume":"278","author":"C Liu","year":"2003","unstructured":"Liu C, Gaca MD, Swenson ES, Vellucci VF, Reiss M, Wells RG (2003) Smads 2 and 3 are differentially activated by transforming growth factor-beta (TGF-beta) in quiescent and activated hepatic stellate cells. Constitutive nuclear localization of Smads in activated cells is TGF-beta-independent. J Biol Chem 278:11721\u201311728","journal-title":"J Biol Chem"},{"key":"2258_CR24","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1002\/hep.22850","volume":"49","author":"OA Gressner","year":"2009","unstructured":"Gressner OA, Lahme B, Siluschek M, Rehbein K, Weiskirchen R, Gressner AM (2009) Connective tissue growth factor is a Smad2 regulated amplifier of transforming growth factor beta actions in hepatocytes\u2013but without modulating bone morphogenetic protein 7 signaling. Hepatology 49:2021\u20132030","journal-title":"Hepatology"},{"key":"2258_CR25","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1128\/MCB.26.2.654-667.2006","volume":"26","author":"W Ju","year":"2006","unstructured":"Ju W, Ogawa A, Heyer J, Nierhof D, Yu L, Kucherlapati R, Shafritz DA, Bottinger EP (2006) Deletion of Smad2 in mouse liver reveals novel functions in hepatocyte growth and differentiation. Mol Cell Biol 26:654\u2013667","journal-title":"Mol Cell Biol"},{"key":"2258_CR26","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1681\/ASN.2009121244","volume":"21","author":"XM Meng","year":"2010","unstructured":"Meng XM, Huang XR, Chung AC, Qin W, Shao X, Igarashi P, Ju W, Bottinger EP, Lan HY (2010) Smad2 protects against TGF-beta\/Smad3-mediated renal fibrosis. J Am Soc Nephrol 21:1477\u20131487","journal-title":"J Am Soc Nephrol"},{"key":"2258_CR27","doi-asserted-by":"crossref","first-page":"17058","DOI":"10.1074\/jbc.M100754200","volume":"276","author":"F Verrecchia","year":"2001","unstructured":"Verrecchia F, Chu ML, Mauviel A (2001) Identification of novel TGF-beta\/Smad gene targets in dermal fibroblasts using a combined cDNA microarray\/promoter transactivation approach. J Biol Chem 276:17058\u201317062","journal-title":"J Biol Chem"},{"key":"2258_CR28","doi-asserted-by":"crossref","first-page":"38502","DOI":"10.1074\/jbc.M107081200","volume":"276","author":"W Yuan","year":"2001","unstructured":"Yuan W, Varga J (2001) Transforming growth factor-beta repression of matrix metalloproteinase-1 in dermal fibroblasts involves Smad3. J Biol Chem 276:38502\u201338510","journal-title":"J Biol Chem"},{"key":"2258_CR29","doi-asserted-by":"crossref","first-page":"19945","DOI":"10.1074\/jbc.M102382200","volume":"276","author":"E Piek","year":"2001","unstructured":"Piek E, Ju WJ, Heyer J, Escalante-Alcalde D, Stewart CL, Weinstein M, Deng C, Kucherlapati R, Bottinger EP, Roberts AB (2001) Functional characterization of transforming growth factor beta signaling in Smad2- and Smad3-deficient fibroblasts. J Biol Chem 276:19945\u201319953","journal-title":"J Biol Chem"},{"key":"2258_CR30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1749-6632.2003.tb03205.x","volume":"995","author":"AB Roberts","year":"2003","unstructured":"Roberts AB, Russo A, Felici A, Flanders KC (2003) Smad3: a key player in pathogenetic mechanisms dependent on TGF-beta. Ann N Y Acad Sci 995:1\u201310","journal-title":"Ann N Y Acad Sci"},{"key":"2258_CR31","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.4161\/cc.20546","volume":"11","author":"E Tarasewicz","year":"2012","unstructured":"Tarasewicz E, Jeruss JS (2012) Phospho-specific Smad3 signaling: impact on breast oncogenesis. Cell Cycle 11:2443\u20132451","journal-title":"Cell Cycle"},{"key":"2258_CR32","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.0959-9673.2004.00377.x","volume":"85","author":"KC Flanders","year":"2004","unstructured":"Flanders KC (2004) Smad3 as a mediator of the fibrotic response. Int J Exp Pathol 85:47\u201364","journal-title":"Int J Exp Pathol"},{"key":"2258_CR33","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000320180","volume":"193","author":"A Masszi","year":"2011","unstructured":"Masszi A, Kapus A (2011) Smaddening complexity: the role of Smad3 in epithelial-myofibroblast transition. Cells Tissues Organs 193:41\u201352","journal-title":"Cells Tissues Organs"},{"key":"2258_CR34","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1111\/j.1478-3231.2009.02011.x","volume":"29","author":"G Latella","year":"2009","unstructured":"Latella G, Vetuschi A, Sferra R, Catitti V, D\u2019Angelo A, Zanninelli G, Flanders KC, Gaudio E (2009) Targeted disruption of Smad3 confers resistance to the development of dimethylnitrosamine-induced hepatic fibrosis in mice. Liver Int 29:997\u20131009","journal-title":"Liver Int"},{"key":"2258_CR35","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1083\/jcb.200204088","volume":"158","author":"S Hayes","year":"2002","unstructured":"Hayes S, Chawla A, Corvera S (2002) TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. J Cell Biol 158:1239\u20131249","journal-title":"J Cell Biol"},{"key":"2258_CR36","doi-asserted-by":"crossref","first-page":"4755","DOI":"10.1242\/jcs.00177","volume":"115","author":"Y Hu","year":"2002","unstructured":"Hu Y, Chuang JZ, Xu K, McGraw TG, Sung CH (2002) SARA, a FYVE domain protein, affects Rab5-mediated endocytosis. J Cell Sci 115:4755\u20134763","journal-title":"J Cell Sci"},{"key":"2258_CR37","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/ncb975","volume":"5","author":"GM Guglielmo Di","year":"2003","unstructured":"Di Guglielmo GM, Le Roy C, Goodfellow AF, Wrana JL (2003) Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover. Nat Cell Biol 5:410\u2013421","journal-title":"Nat Cell Biol"}],"container-title":["Molecular and Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11010-014-2258-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11010-014-2258-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11010-014-2258-1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T18:43:37Z","timestamp":1565981017000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11010-014-2258-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,29]]},"references-count":37,"journal-issue":{"issue":"1-2","published-print":{"date-parts":[[2015,2]]}},"alternative-id":["2258"],"URL":"https:\/\/doi.org\/10.1007\/s11010-014-2258-1","relation":{},"ISSN":["0300-8177","1573-4919"],"issn-type":[{"value":"0300-8177","type":"print"},{"value":"1573-4919","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,29]]}}}