Expression of SPARC by activated hepatic stellate cells and its correlation with the stages of fibrogenesis in human chronic hepatitis

Abstract

Secreted protein, acidic and rich in cysteine (SPARC), which functions in tissue remodeling, has been reported to be expressed by myofibroblasts in liver cirrhosis and hepatocellular carcinoma. This study aimed to reveal its expression in chronic hepatitis. Immuno-light and electron microscopy demonstrated that SPARC was expressed by nerve fibers and hepatic stellate cells (HSCs) in the liver parenchyma and myofibroblasts in the fibrous septa. Reaction products were localized in the rough endoplasmic reticulum and nuclear envelope. Serial section analysis demonstrated that SPARC, platelet-derived growth factor receptor-beta, and alpha-smooth muscle actin were co-expressed by HSCs. Quantitative analysis demonstrated that, while SPARC-positive HSCs were sparse in control livers, they significantly increased in number in the livers with chronic hepatitis. There were, however, no significant differences in number among the grades of activity, the stages of fibrosis, or etiology (virus-infected or autoimmune, hepatitis B virus or hepatitis C virus). In liver cirrhosis, however, they significantly decreased in number. The present results indicate that SPARC is expressed by activated HSCs in chronic hepatitis, suggesting the involvement of SPARC in hepatic fibrogenesis after chronic injuries.

SPARC Oppositely Regulates Inflammation and Fibrosis in Bleomycin-Induced Lung Damage

“…The matricellular glycoprotein termed secreted protein acidic and rich in cysteine (SPARC) has a key role in extracellular matrix (ECM) assembly and molding. Consistently, SPARC has been implicated in the pathogenesis of several fibrotic disorders, such as adipose tissue fibrosis, 1 hepatic fibrosis, 2,3 lung fibrosis, 4 and scleroderma. 5 This notion comes from data generated in Sparc Ϫ/Ϫ mice or gene-silencing strategies in models of skin, liver, and pulmonary fibrosis.…”

Stimulation of Proliferation of Rat Hepatic Stellate Cells by Galectin-1 and Galectin-3 through Different Intracellular Signaling Pathways

“…Immunohistochemistry-Immunohistochemical detection of galectin-1 and galectin-3 in rat liver tissues was performed according to the method described in detail by Nakatani et al (42). Immunoprecipitates were visualized using 0.025% 3,3Ј-diaminobenzidine tetrahydrochloride and 0.003% H 2 O 2 .…”

Reversibility of fibrosis, inflammation, and endoplasmic reticulum stress in the liver of rats fed a methionine–choline-deficient diet

“…Immunohistochemistry was performed according to the methods described elsewhere. 26 Briefly, sections were deparaffinized, washed, and preincubated in blocking solution, followed by incubation with anti-4-HNE (15 mg/ml), HO-1 (1:50), CD68 (1:100), a-SMA (1:100), cytoglobin (1:400), or caspase-12 (1:100) antibodies. Sections were then incubated with HRP-conjugated secondary antibodies (1:1000), washed, covered with DAB, and counterstained with hematoxylin.…”