Fibrosis

Is it a coactivator disease?

Asish K Ghosh*, Douglas E Vaughan

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Fibrosis is an abnormal fibroblast-activationassociated pathological manifestation in injured organs where excessive non-physiological synthesis and accumulation of extracellular matrix (ECM) proteins by activated/differentiated fibroblasts disrupts tissue homeostasis. Like other eukaryotic genes, expression of ECM protein genes not only depends on its gene sequences in the regulatory region but also influenced by non-genetic factors called epigenetic regulators including acetyltransferases, deacetylases, methyltransferases and microRNAs. The acetyltransferase p300 (ATp300), a transcriptional coactivator, is a major player in the epigenetic regulation of genes whose products are involved in cellular growth, proliferation, apoptosis and essential for embryonic development. ATp300 acetylates specific lysine residues in histones and transcription factors (KAT) and as a transcriptional coactivator it forms a bridge between upstream regulatory element binding protein complex and basal transcriptional machinery. Abnormal coactivator activity-associated diseases are known as coactivator diseases. Abnormalities in ATp300 activities in adults are associated with numerous diseases. Here, we review the significant roles of ATp300 in epigenetic regulation of collagen synthesis and deposition in extracellular spaces, matrix remodeling and tissue fibrogenesis. The present day understanding on the distinct role of acetyltransferases, deacetylases, and deacetylase inhibitors on epigenetic regulation of matrix remodeling and fibrosis has also been discussed.

Original languageEnglish (US)
Pages (from-to)1556-1570
Number of pages15
JournalFrontiers in Bioscience - Elite
Volume4 E
Issue number4
StatePublished - Jan 1 2012

Fingerprint

Epigenomics
Fibrosis
Acetyltransferases
Genes
Extracellular Matrix Proteins
Fibroblasts
Tissue homeostasis
Nucleic Acid Regulatory Sequences
Methyltransferases
Extracellular Space
MicroRNAs
Gene expression
Histones
Lysine
Machinery
Embryonic Development
Extracellular Matrix
Carrier Proteins
Homeostasis
Transcription Factors

Keywords

  • Coactivator ATp300
  • Collagen
  • Epigenetics
  • HDAC
  • PAI-1
  • Review
  • TGF-beta
  • Tissue fibrosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

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title = "Fibrosis: Is it a coactivator disease?",
abstract = "Fibrosis is an abnormal fibroblast-activationassociated pathological manifestation in injured organs where excessive non-physiological synthesis and accumulation of extracellular matrix (ECM) proteins by activated/differentiated fibroblasts disrupts tissue homeostasis. Like other eukaryotic genes, expression of ECM protein genes not only depends on its gene sequences in the regulatory region but also influenced by non-genetic factors called epigenetic regulators including acetyltransferases, deacetylases, methyltransferases and microRNAs. The acetyltransferase p300 (ATp300), a transcriptional coactivator, is a major player in the epigenetic regulation of genes whose products are involved in cellular growth, proliferation, apoptosis and essential for embryonic development. ATp300 acetylates specific lysine residues in histones and transcription factors (KAT) and as a transcriptional coactivator it forms a bridge between upstream regulatory element binding protein complex and basal transcriptional machinery. Abnormal coactivator activity-associated diseases are known as coactivator diseases. Abnormalities in ATp300 activities in adults are associated with numerous diseases. Here, we review the significant roles of ATp300 in epigenetic regulation of collagen synthesis and deposition in extracellular spaces, matrix remodeling and tissue fibrogenesis. The present day understanding on the distinct role of acetyltransferases, deacetylases, and deacetylase inhibitors on epigenetic regulation of matrix remodeling and fibrosis has also been discussed.",
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Fibrosis : Is it a coactivator disease? / Ghosh, Asish K; Vaughan, Douglas E.

In: Frontiers in Bioscience - Elite, Vol. 4 E, No. 4, 01.01.2012, p. 1556-1570.

Research output: Contribution to journalArticle

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AU - Vaughan, Douglas E

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AB - Fibrosis is an abnormal fibroblast-activationassociated pathological manifestation in injured organs where excessive non-physiological synthesis and accumulation of extracellular matrix (ECM) proteins by activated/differentiated fibroblasts disrupts tissue homeostasis. Like other eukaryotic genes, expression of ECM protein genes not only depends on its gene sequences in the regulatory region but also influenced by non-genetic factors called epigenetic regulators including acetyltransferases, deacetylases, methyltransferases and microRNAs. The acetyltransferase p300 (ATp300), a transcriptional coactivator, is a major player in the epigenetic regulation of genes whose products are involved in cellular growth, proliferation, apoptosis and essential for embryonic development. ATp300 acetylates specific lysine residues in histones and transcription factors (KAT) and as a transcriptional coactivator it forms a bridge between upstream regulatory element binding protein complex and basal transcriptional machinery. Abnormal coactivator activity-associated diseases are known as coactivator diseases. Abnormalities in ATp300 activities in adults are associated with numerous diseases. Here, we review the significant roles of ATp300 in epigenetic regulation of collagen synthesis and deposition in extracellular spaces, matrix remodeling and tissue fibrogenesis. The present day understanding on the distinct role of acetyltransferases, deacetylases, and deacetylase inhibitors on epigenetic regulation of matrix remodeling and fibrosis has also been discussed.

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