Lumican, an extracellular matrix proteoglycan, is a novel requisite for hepatic fibrosis

Anuradha Krishnan, Xia Li, Winstonwhei Yang Kao, Kimberly Viker, Kim Butters, Howard Masuoka, Bruce Knudsen, Gregory Gores, Michael Charlton

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Lumican, an extracellular matrix proteoglycan was previously shown to be upregulated with increasing severity of nonalcoholic steatohepatitis (NASH). Although lumican is involved in collagen fibrillogenesis in extra-hepatic tissues, little is known about the role of lumican in hepatic disease. We therefore determined lumican expression in etiologies other than clinical NASH. Our results indicated that lumican is upregulated in clinical samples of hepatitis C virus infection, in experimental rodent models of chronic and acute liver injury and could additionally be induced in vitro in response to the pro-fibrotic cytokine transforming growth factor β1 (TGFβ1) and to lipotoxic palmitic acid. Together, these results suggested a role for lumican in hepatic fibrosis. To investigate the functional role of lumican in hepatic fibrosis, lumican null (Null) and wild-type (WT) littermates were administered carbon tetrachloride intra-peritoneally. Serum and liver tissue were analyzed for indices of liver injury, fibrosis, matrix turnover, and proliferation. Hepatic fibrosis was greatly reduced in null animals (P

Original languageEnglish (US)
Pages (from-to)1712-1725
Number of pages14
JournalLaboratory Investigation
Volume92
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

Fingerprint

Proteoglycans
Extracellular Matrix
Fibrosis
Liver
Palmitic Acid
Lumican
Carbon Tetrachloride
Wounds and Injuries
Transforming Growth Factors
Virus Diseases
Hepacivirus
Liver Cirrhosis
Rodentia
Theoretical Models
Collagen
Cytokines
Serum

Keywords

  • arbon tetrachloride
  • collagen
  • extracellular matrix
  • hepatic fibrosis
  • lumican
  • proteoglycan
  • transforming growth factor β1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

Cite this

Lumican, an extracellular matrix proteoglycan, is a novel requisite for hepatic fibrosis. / Krishnan, Anuradha; Li, Xia; Kao, Winstonwhei Yang; Viker, Kimberly; Butters, Kim; Masuoka, Howard; Knudsen, Bruce; Gores, Gregory; Charlton, Michael.

In: Laboratory Investigation, Vol. 92, No. 12, 12.2012, p. 1712-1725.

Research output: Contribution to journalArticle

Krishnan, A, Li, X, Kao, WY, Viker, K, Butters, K, Masuoka, H, Knudsen, B, Gores, G & Charlton, M 2012, 'Lumican, an extracellular matrix proteoglycan, is a novel requisite for hepatic fibrosis', Laboratory Investigation, vol. 92, no. 12, pp. 1712-1725. https://doi.org/10.1038/labinvest.2012.121
Krishnan, Anuradha ; Li, Xia ; Kao, Winstonwhei Yang ; Viker, Kimberly ; Butters, Kim ; Masuoka, Howard ; Knudsen, Bruce ; Gores, Gregory ; Charlton, Michael. / Lumican, an extracellular matrix proteoglycan, is a novel requisite for hepatic fibrosis. In: Laboratory Investigation. 2012 ; Vol. 92, No. 12. pp. 1712-1725.
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