Search Results to Barbara D. Smith, PhD

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Research Expertise & Professional Interests The primary goal in our laboratory is to establish a better understanding of the mechanisms involved in the control of collagen gene expression associated with inflammation, atherosclerosis, tumors, and fibrotic diseases including systemic sclerosis. Collagen, a family of extracellular proteins, plays a critical role in remodeling after injury. Progressive deposition of excess extracellular matrix (ECM), occurs in a large group of diseases with no effective therapy including cardiovascular disease, pulmonary fibrosis, diabetic nephropathy, systemic sclerosis, and liver cirrhosis. Fibrosis (excessive scarring) is a progressive deposition of excess collagen-rich extracellular matrix produced by activated myofibroblasts leading to impairment and finally failure of affected organs. In normal healing following injury, fibroblasts differentiate into myofibroblasts. If progression to fibrosis occurs, these myofibroblasts do not undergo apoptosis but instead continue to proliferate and produce excess amounts of ECM. Isolated primary fibroblasts from fibrotic lesions maintain their activated myofibroblast phenotype containing abundant stress fibers with smooth muscle actin (SMA). Myocardin related transcription factors (MRTF-A, MRTF-B), members of the myocardin family, link actin dynamics with gene transcription. Our data indicate that MRTF-A dramatically (100 fold) activates collagen transcription. Fibroblasts with knockdown of MRTFA have different morphology and produce less collagen and SMA. We hypothesize that MRTFA plays a central role in activation and perpetuation of myofibroblast during the development of fibrotic disease. Our laboratory has been examining both activation and repression of collagen transcription using molecular biology approaches. We have demonstrated that collagen type I genes are methylated in the first exon in cancer cells and colon cancer. Collagen gene is silenced in certain tumors. A methylation sensitive DNA binding protein (RFX1) represses transcription by binding to the collagen gene transcription start site. This protein belongs to a family of proteins that can function as transcription activators or repressors. RFX1 interacts with a co-repressor complex containing histone deacetylase which could be involved with spreading of DNA methylation and silencing. A RFX5 complex containing three other proteins (RFXANK/B, RFXAP, CIITA) are essential activators of major histocompatibility complex class II (MHC II) proteins that respond to interferon-gamma during inflammation and activate cells to become antigen producing cells. Interferon activates RFX5/CIITA synthesis and nuclear localization in human fibroblasts and smooth muscle cells. RFX5 proteins form a complex at the RFX site at the collagen gene transcription start site and recruits CIITA to repress collagen transcription through a phosphorylation sensitive interaction with co-repressor complex. Thus, this family of proteins may be very important modulators of collagen expression during inflammation.
Self-Described Keywords transcription factors

One or more keywords matched the following items that are connected to Smith, Barbara

Item TypeName
Concept Transcription Factors
Concept Transcription, Genetic
Concept Transcriptional Activation
Concept Sp1 Transcription Factor
Concept Transcription Initiation Site
Concept Transcription Factor AP-2
Concept NFI Transcription Factors
Academic Article Regulation of the alpha 1(I) collagen promoter via a transforming growth factor-beta activation element.
Academic Article Methylation in the initiation region of the first exon suppresses collagen pro-alpha2(I) gene transcription.
Academic Article A methylation-responsive MDBP/RFX site is in the first exon of the collagen alpha2(I) promoter.
Academic Article A member of the Y-box protein family interacts with an upstream element in the alpha1(I) collagen gene.
Academic Article The RFX family interacts at the collagen (COL1A2) start site and represses transcription.
Academic Article Discordant regulation of human type I collagen genes by prostaglandin E2.
Academic Article DNA hypermethylation near the transcription start site of collagen alpha2(I) gene occurs in both cancer cell lines and primary colorectal cancers.
Academic Article DNA methylation inhibits transcription of procollagen alpha 2(I) promoters.
Academic Article Interferon gamma repression of collagen (COL1A2) transcription is mediated by the RFX5 complex.
Academic Article Major histocompatibility class II transactivator (CIITA) mediates repression of collagen (COL1A2) transcription by interferon gamma (IFN-gamma).
Academic Article Transforming-growth-factor-beta activation elements in the distal promoter regions of the rat alpha 1 type I collagen gene.
Academic Article Collagen alpha1(I) gene (COL1A1) is repressed by RFX family.
Academic Article Regulatory factor for X-box family proteins differentially interact with histone deacetylases to repress collagen alpha2(I) gene (COL1A2) expression.
Academic Article Collagen and major histocompatibility class II expression in mesenchymal cells from CIITA hypomorphic mice.
Academic Article Peroxisome proliferator-activated receptor gamma interacts with CIITA x RFX5 complex to repress type I collagen gene expression.
Academic Article CIITA mediates interferon-gamma repression of collagen transcription through phosphorylation-dependent interactions with co-repressor molecules.
Academic Article The differential effect of prostaglandin E2 on transforming growth factor-beta and insulin-induced collagen formation in lung fibroblasts.
Academic Article Myocardin-related transcription factor-A complexes activate type I collagen expression in lung fibroblasts.
Academic Article Methylation of the alpha 2(I) collagen gene in chemically transformed rat liver epithelial cells.
Academic Article A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma Related Fibrosis.
Academic Article Myocardin-related transcription factor A regulates conversion of progenitors to beige adipocytes.
Academic Article CIITA represses collagen transcription and activates MHC II
Academic Article The protein arginine methyltransferase (PRMT5) associates with class II transactivator (CIITA) to repress collagen transcription

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