{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:42:24Z","timestamp":1791254544864,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,7,25]],"date-time":"2003-07-25T00:00:00Z","timestamp":1059091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In response to tissue injury connective tissue synthesis occurs either normally or abnormally, which is mediated by transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) and other growth factors. This article will be primarily concerned with the response of injured tissues at the gene level of Type I procollagen synthesis in response to TGF\u2010\u03b2. This leads to provisional repair, which in turn may lead to involution, remodeling, regeneration, and ultimately repair. Alternately, continuation of provisional repair may lead to fibrosis and ultimately scarring. Scarring of internal organs such as the liver and the lung leads to loss of function and ultimately death. In the case of scarring of skin, this is a cosmetic problem and can be rectified by surgery. Type I procollagen is synthesized by two genes, <jats:italic>pro\u03b11<\/jats:italic> (Type I) and <jats:italic>pro\u03b12<\/jats:italic> (Type I) collagen genes. This article will focus on DNA binding sites on these two genes, which regulate the transcription of the specific gene. This article will also define specific cell signaling pathways for the turning on of the <jats:italic>pro\u03b11<\/jats:italic> and <jats:italic>pro\u03b12<\/jats:italic> (Type I) collagen genes. This article will address several questions. First, what is the major cytokine acting extracellularly which stimulates the transcription of the <jats:italic>pro\u03b11<\/jats:italic> and <jats:italic>pro\u03b12<\/jats:italic> (Type I) collagen genes during tissue fibrosis? Secondly, how are the signals transmitted by the extracellular profibrotic cytokine TGF\u2010\u03b2 from the cellular membrane to the nucleus for transcription of the <jats:italic>pro\u03b11<\/jats:italic> (Type I) and <jats:italic>pro\u03b12<\/jats:italic> (Type I) collagen genes? Thirdly, what signaling pathways cross\u2010talk with the signaling pathways resulting in the expression of the Type I collagen genes? Fourthly, how does TGF\u2010\u03b2 affect extracellular matrix homeostasis? Fifthly, what are the nuclear factors corresponding to the DNA elements required for the promotion of the <jats:italic>pro\u03b11<\/jats:italic> (Type I) and <jats:italic>pro\u03b12<\/jats:italic> (Type I) collagen genes? Finally, how are the <jats:italic>pro\u03b11<\/jats:italic> (Type I) and <jats:italic>pro\u03b12<\/jats:italic> (Type I) collagen genes coordinately regulated? Strategies will also be presented for reducing fibrosis, which is the result of overexpression of TGF\u2010\u03b2. J. Cell. Biochem. 90: 1\u20135, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.10599","type":"journal-article","created":{"date-parts":[[2003,8,22]],"date-time":"2003-08-22T14:28:18Z","timestamp":1061562498000},"page":"1-5","source":"Crossref","is-referenced-by-count":80,"title":["How is Type I procollagen synthesis regulated at the gene level during tissue fibrosis"],"prefix":"10.1002","volume":"90","author":[{"given":"Kenneth R.","family":"Cutroneo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,8,18]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/153537020222701102"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.6.3272"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007206014638"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10528"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010133200"},{"key":"e_1_2_2_7_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1042\/bj3360373","article-title":"chk\u2010YB\u20101b, a Y\u2010box binding protein activates transcription from rat alpha(I) procollagen gene promoter","volume":"336","author":"Dhalla AK","year":"1998","journal-title":"Biochem J"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.12.6813"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212334200"},{"key":"e_1_2_2_10_1","doi-asserted-by":"crossref","first-page":"14828","DOI":"10.1016\/S0021-9258(17)36699-1","article-title":"Transforming growth factor\u2010\u03b2 stimulates \u03b12(I) collagen gene expression through a cis\u2010acting element that contains an SP\u20101\u2010binding site","volume":"269","author":"Inagaki Y","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010485200"},{"key":"e_1_2_2_12_1","doi-asserted-by":"crossref","first-page":"13156","DOI":"10.1016\/S0021-9258(17)36812-6","article-title":"Bleomycin stimulates pro\u2010\u03b1\u03b11(I) collagen promoter through transforming growth factor \u03b2 response element by intracellular and extracellular signaling","volume":"269","author":"King SL","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(98)80069-5"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206535200"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(02)00058-X"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.7.1101"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-0436.1995.5820149.x"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-475X.1999.00133.x"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10413"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(98)00198-1"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(02)00082-7"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.10599","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.10599","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T18:03:26Z","timestamp":1697220206000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.10599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,8,18]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,9]]}},"alternative-id":["10.1002\/jcb.10599"],"URL":"https:\/\/doi.org\/10.1002\/jcb.10599","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,8,18]]}}}