SPARC: a Ca2+-binding extracellular protein associated with endothelial cell injury and proliferation

Sage, Helene; Decker, Jay D.; Funk, Sarah E.; Chow, M

doi:10.1016/0022-2828(89)90833-x

Cited by 39 publications

(20 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SPARC is a calcium-binding protein secreted by a number of cells, including fibroblasts, endothelial cells, and osteoblasts (Stenner et al 1986;Sage et al 1989a;Kasugai et al 1991;Vuorio et al 2003). SPARC is expressed in many tissues during development, whereas a Data are expressed as mean Ϯ SD ( n ) where n ϭ number of discs evaluated.…”

Section: Discussionmentioning

confidence: 99%

Targeted Deletion of the SPARC Gene Accelerates Disc Degeneration in the Aging Mouse

Gruber

Sage

Norton³

et al. 2005

J Histochem Cytochem.

View full text Add to dashboard Cite

S U M M A R Y SPARC (secreted protein, acidic, and rich in cysteine) is a matricellular protein that is present in the intervertebral disc; in man, levels of SPARC decrease with aging and degeneration. In this study, we asked whether targeted deletion of SPARC in the mouse influenced disc morphology. SPARC-null and wild-type (WT) mice were studied at 0.3-21 months of age. Radiologic examination of spines from 2-month-old SPARC-null mice revealed wedging, endplate calcification, and sclerosis, features absent in age-matched WT spines. Discs from 3-month-old SPARC-null mice had a greater number of annulus cells than those of WT animals (1884.6 Ϯ 397.9 [mean Ϯ SD] vs 1500.2 Ϯ 188.2, p ϭ 0.031). By 19 months discs from SPARC-null mice contained fewer cells than WT counterparts (1383.6 Ϯ 363.3 vs 1466.8 Ϯ 148.0, p ϭ 0.033). Histology of midsagittal spines showed herniations of lower lumbar discs of SPARC-null mice ages 14-19 months; in contrast, no herniations were seen in WT age-matched animals. Ultrastructural studies showed uniform collagen fibril diameters in the WT annulus, whereas in SPARC-null disc fibrils were of variable size with irregular margins. Consistent with the connective tissue deficits observed in other tissues of SPARC-null mice, our findings support a fundamental role for SPARC in the production, assembly, or maintenance of the disc extracellular matrix.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeted Deletion of the SPARC Gene Accelerates Disc Degeneration in the Aging Mouse

Gruber

Sage

Norton³

et al. 2005

J Histochem Cytochem.

View full text Add to dashboard Cite

show abstract

“…Matricellular proteins represent a unique group of proteins, and secreted protein acidic and rich in cysteine is increased in both BE and EAC. Secreted protein acidic and rich in cysteine demonstrates counter-adhesive and anti-proliferative functions and can modify the cell cycle and remodel matrix [67]. It is thought to be overexpressed in the tumor microenvironment in an attempt to inhibit tumor growth [7].…”

Section: Inflammation and Immune Modulation Of The Tumor Microenvironmentmentioning

confidence: 99%

The role of inflammation in cancer of the esophagus

O’Sullivan

Phelan

O’Hanlon

et al. 2014

Expert Review of Gastroenterology & Hepatology

View full text Add to dashboard Cite

Esophageal adenocarcinoma is the eighth most common malignancy worldwide. The overall prognosis is poor, with 5-year survival ranges of approximately 15-25%, and 30-50% for patients who can be treated with curative intent. There has been a marked increase in incidence of esophageal adenocarcinoma over the last 30 years, with chronic and severe reflux, diet and obesity identified as principal factors fuelling this rise in the West. Esophageal adenocarcinoma is an exemplar model of an inflammation-associated cancer. The key molecular pathways driving tumor development and influencing tumor biology are the subject of considerable research efforts, and is the principal focus of this review. In addition, the diverse range of changes occurring in the local immune response, tissue microenvironment, metabolic profile, intracellular signaling mechanisms and microRNA signatures are discussed, as well as novel targeted therapies.

show abstract

“…We examined the potential contribution of such proteinases to MCAA-associated fibrosis. The matricellular glycoprotein SPARC (secreted protein acidic and rich in cysteine) is expressed during development and tissue remodeling and repair (Sage et al, 1989a,b) and mediates pro-collagen processing and assembly into fibrils (Harris et al, 2011; Rentz et al, 2007). Additionally, SPARC has been implicated in collagen protein expression and accumulation in bleomycin-induced pulmonary fibrosis (Strandjord et al, 1999; Wang et al, 2010) and following asbestos exposure (Pershouse et al, 2009; Wang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Asbestos-associated mesothelial cell autoantibodies promote collagen depositionin vitro

Serve¹,

Black²,

Szeinuk³

et al. 2013

Inhalation Toxicology

View full text Add to dashboard Cite

Fibrosis, characterized by excessive collagen protein deposition, is a progressive disease that can fatally inhibit organ function. Prolonged exposure to pathogens or environmental toxicants such as asbestos can lead to chronic inflammatory responses associated with fibrosis. Significant exposure to amphibole asbestos has been reported in and around Libby, Montana due to local mining of asbestos-contaminated vermiculite. These exposures have been implicated in a unique disease etiology characterized predominantly by pleural disorders, including fibrosis. We recently reported the discovery of mesothelial cell autoantibodies (MCAAs) in the sera of Libby residents and demonstrated a positive and significant correlation with pleural disease; however, a mechanistic link was not determined. Here we demonstrate that MCAAs induce pleural mesothelial cells to produce a collagen matrix but do not affect production of the pro-inflammatory cytokine tumor growth factor-β. While autoantibodies commonly induce a pro-fibrotic state by inducing epithelial–mesenchymal transition (EMT) of target cells, we found no evidence supporting EMT in cells exposed to MCAA positive human sera. Although implicated in other models of pulmonary fibrosis, activity of the protein SPARC (secreted protein, acidic and rich in cysteine) did not affect MCAA-induced collagen deposition. However, matrix formation was dependent on matrix metalloproteinase (MMP) activity, and we noted increased expression of MMP-8 and -9 in supernatants of mesothelial cells incubated with MCAA positive sera compared to control. These data suggest a mechanism by which MCAA binding leads to increased collagen deposition through altering MMP expression and provides an important mechanistic link between MCAAs and asbestos-related, autoimmune-induced pleural fibrosis.

show abstract

SPARC: a Ca2+-binding extracellular protein associated with endothelial cell injury and proliferation

Cited by 39 publications

References 27 publications

Targeted Deletion of the SPARC Gene Accelerates Disc Degeneration in the Aging Mouse

Targeted Deletion of the SPARC Gene Accelerates Disc Degeneration in the Aging Mouse

The role of inflammation in cancer of the esophagus

Asbestos-associated mesothelial cell autoantibodies promote collagen depositionin vitro

Contact Info

Product

Resources

About