Biglycan and Decorin Gene Expression in Normal and Fibrotic Rat Liver: Cellular Localization and Regulatory Factors

Abstract

The expression of genes encoding the core proteins of the novel small chondroitin/dermatan sulfate proteoglycans decorin and biglycan was studied in the livers of normal rats and in liver tissue during fibrogenesis induced by prolonged bile-duct ligation and thioacetamide poisoning. The cell types responsible for the expression of these transcripts and some key regulatory factors were identified. Both biglycan and decorin messenger RNAs were detected in normal liver tissue. Their relative abundance increased strongly during liver fibrogenesis, reaching highest levels in cirrhotic tissue 8 wk after common bile-duct ligation and after 12 wk of peroral thioacetamide administration, respectively. Specific proteoglycan transcripts were almost absent in hepatocytes from normal and regenerating liver, and only trace amounts were observed in freshly isolated and cultured Kupffer cells. Fat-storing cells clearly expressed both biglycan and decorin transcripts. The steady-state levels of their messenger RNAs increased threefold (biglycan) and fourfold (decorin) during primary culture. Myofibroblastlike cells (transformed fat-storing cells after the second passage) contained dramatically reduced levels of decorin messenger RNA and also lower levels of biglycan messenger RNA compared with primary cultures. These changes of core protein messenger RNA expression were not reflected by the synthesis rates of medium proteoglycans labeled with 35S as Na2SO4, in particular that of medium chondroitin sulfate. Transiently acidified (but not native) conditioned media from Kupffer cells and myofibroblastlike cells and transforming growth factor-beta 1 enhanced the relative abundances of biglycan and decorin messenger RNAs up to five times in primary-cultured fat-storing cells. Biglycan and decorin in myofibroblastlike cells did not respond to these stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of transforming growth factor β response and signaling during transdifferentiation of rat hepatic stellate cells to myofibroblasts

“…58 In MFBs, decorin and biglycan, which are already present at relatively high levels in untreated cells, cannot be increased further by TGF-␤1. Another cytokine, tumor necrosis factor ␣, however, can superinduce both mRNAs in MFBs.…”

Differential expression of keratan sulphate proteoglycans fibromodulin, lumican and aggrecan in normal and fibrotic rat liver

“…Both biglycan and decorin are expressed in the rat liver, albeit at different basal levels, with an increase paralleling the development of fibrosis [20]. Eumican is also expressed in the rat liver, but at quite constant levels throughout the fibrotic process.…”

Stimulation of inducible nitric oxide synthase in rat liver by hyaluronan fragments

“…[22][23][24][25][26] HA is a prominent component of the expanded extracellular matrix in the injured liver, and is markedly overproduced in experimental liver injury. 42 Of note, HA levels are also elevated in patients with alcoholic hepatitis and may correlate with the clinical severity of liver disease.…”

“…In chronically injured liver, matrix components produced in increased quantities include interstitial collagens, laminins, fibronectins, proteoglycans and glycosaminoglycans (heparan sulfate, chondroitin sulfate). [22][23][24][25][26] Among the glycosaminoglycan components produced in excess in fibrosing liver disease is HA. 23 Several studies have established that HA is the principal ligand for CD44.…”