Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats

Abe, Hiroo; Uto, Hirofumi; Takami, Yoichiro; Takahama, Yuka; Hasuike, Satoru; Kodama, Mayumi; Nagata, Kenji; Moriuchi, Akihiro; Numata, Masatsugu; Ido, Akio; Tsubouchi, Hirohito

doi:10.1016/j.bbrc.2007.03.035

Cited by 33 publications

(25 citation statements)

References 20 publications

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“…However, Gpnmb may act as a feedback regulator of cardiac inflammation and fibrosis in mice with TMEV-induced myocarditis, because Gpnmb has been shown to regulate proinflammatory responses and hepatic fibrosis in vivo. 51,52 In PCA, Bmp10 contributed most to PC1 values based on the factor loading for PC1. Bmp10 is a member of transforming growth factor-β and plays a critical role in regulating the development of the heart.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Multivariate Analysis Determined a Set of Phase-Specific Biomarker Candidates in a Novel Mouse Model for Viral Myocarditis

Omura

Kawai

Sato

et al. 2014

Circ Cardiovasc Genet

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Background Myocarditis is an inflammatory disease of the cardiac muscle and is mainly caused by viral infections. Viral myocarditis has been proposed to be divided into 3 phases: the acute viral phase, the subacute immune phase, and the chronic cardiac remodeling phase. Although individualized therapy should be applied depending on the phase, no clinical or experimental studies have found biomarkers that distinguish between the 3 phases. Theiler’s murine encephalomyelitis virus belongs to the genus Cardiovirus and can cause myocarditis in susceptible mouse strains. Methods and Results Using this novel model for viral myocarditis induced with Theiler’s murine encephalomyelitis virus, we conducted multivariate analysis including echocardiography, serum troponin and viral RNA titration, and microarray to identify the biomarker candidates that can discriminate the 3 phases. Using C3H mice infected with Theiler’s murine encephalomyelitis virus on 4, 7, and 60 days post infection, we conducted bioinformatics analyses, including principal component analysis and k-means clustering of microarray data, because our traditional cardiac and serum assays, including 2-way comparison of microarray data, did not lead to the identification of a single biomarker. Principal component analysis separated heart samples clearly between the groups of 4, 7, and 60 days post infection. Representative genes contributing to the separation were as follows: 4 and 7 days post infection, innate immunity–related genes, such as Irf7 and Cxcl9; 7 and 60 days post infection, acquired immunity–related genes, such as Cd3g and H2-Aa; and cardiac remodeling–related genes, such as Mmp12 and Gpnmb. Conclusions Sets of molecules, not single molecules, identified by unsupervised principal component analysis, were found to be useful as phase-specific biomarkers.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics Multivariate Analysis Determined a Set of Phase-Specific Biomarker Candidates in a Novel Mouse Model for Viral Myocarditis

Omura

Kawai

Sato

et al. 2014

Circ Cardiovasc Genet

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“…The osteoinductive effects of BMP-2 are dependent on OA (Abdelmagid et al, 2007). OA has the ability to regulate cell proliferation, adhesion, differentiation and synthesis of ECM proteins in various cell types (Adema et al, 1994; Jager et al, 2000; Anderson et al, 2001, 2002, 2006; Safadi et al, 2001; Bandari et al, 2003; Onaga et al, 2003; Ott et al, 2003; Safadi et al, 2003; Yasumoto et al, 2004; Boissy et al, 2005; Ogawa et al, 2005; Okamoto et al, 2005; Brunberg et al, 2006; Hoashi et al, 2006; Abe et al, 2007; Helip-Wooley et al, 2007; Nakamura et al, 2007; Ripoll et al, 2007). OA messenger ribonucleic acid (mRNA) and protein are expressed by human and rodent osteoblasts (Safadi et al, 2001; Owen et al, 2003).…”

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confidence: 99%

Comparison of bone morphogenetic protein‐2 and osteoactivin for mesenchymal cell differentiation: Effects of bolus and continuous administration

Arosarena¹,

Carpio-Cano²,

Cadena³

et al. 2011

Journal Cellular Physiology

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Current osteoinductive protein therapy utilizes bolus administration of large doses of bone morphogenetic proteins (BMPs), which is costly, and may not replicate normal bone healing. The limited in vivo biologic activity of BMPs requires the investigation of growth factors that may enhance this activity. In this study, we utilized the C3H10T1/2 murine mesenchymal stem cell line to test the hypotheses that osteoactivin (OA) has comparable osteoinductive effects to bone morphogenetic protein-2 (BMP-2), and that sustained administration of either growth factor would result in increased osteoblastic differentiation as compared to bolus administration. Sustained release biodegradable hydrogels were designed, and C3H10T1/2 cells were grown on hydrogels loaded with BMP-2 or OA. Controls were grown on unloaded hydrogels, and positive controls were exposed to bolus growth factor administration. Cells were harvested at several time points to assess osteoblastic differentiation. Alkaline phosphatase (ALP) staining and activity, and gene expression of ALP and osteocalcin were assessed. Treatment with OA or BMP-2 resulted in comparable effects on osteoblastic marker expression. However, cells grown on hydrogels demonstrated osteoblastic differentiation that was not as robust as cells treated with bolus administration. This study shows that OA has comparable effects to BMP-2 on osteoblastic differentiation using both bolus administration and continuous release, and that bolus administration of OA has a more profound effect than administration using hydrogels for sustained release. This study will lead to a better understanding of appropriate delivery methods of osteogenic growth factors like OA for repair of fractures and segmental bone defects.

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“…The gene encoding Gpnmb was isolated in our previous study, and was differentially expressed in the livers of rats fed a choline-deficient, L-amino acid-defined diet (19). In addition, our previous investigations demonstrated that transgenic Gpnmb expression attenuates the development of hepatic fibrosis (20). Previous studies have demonstrated that the expression of Gpnmb in macrophages functions as a feedback regulator of pro-inflammatory responses (21), and that the binding of Gpnmb on antigen-presenting cells to syndecan-4 on activated T cells inhibits T-cell activation (22).…”

Section: Introductionmentioning

confidence: 99%

Expression of glycoprotein nonmetastatic melanoma protein B in macrophages infiltrating injured mucosa is associated with the severity of experimental colitis in mice

Sasaki

Kumagai

Uto

et al. 2015

Molecular Medicine Reports

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Abstract. Glycoprotein nonmetastatic melanoma protein B (Gpnmb) is a transmembrane glycoprotein, which negatively regulates the inflammatory responses of macrophages. However, the role of Gpnmb in intestinal macrophages remains to be fully elucidated. The present study aimed to investigate the expression of Gpnmb and its effects on colonic mucosal injuries associated with dextran sulfate sodium (DSS)-induced colitis in BALB/c mice, DBA/2J (D2) mice lacking Gpnmb and Gpnmb-transgenic DBA/2J mice (D2-gpnmb+). The colonic expression of Gpnmb increased with the severity of DSS-induced colitis in BALB/c mice, and macrophages infiltrating the inflamed mucosa were found to express Gpnmb. The D2 mice lacking Gpnmb exhibited more severe DSS-induced colitis, which was accompanied by higher levels of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6, compared with the D2-gpnmb+ mice. Following lipopolysaccharide stimulation, macrophages from the D2 mice expressed higher levels of pro-inflammatory cytokines and lower levels of IL-10, compared with the D2-gpnmb+mice. In addition, in the RAW264.7 murine macrophage cell line, knockdown of Gpnmb by small interfering RNA was associated with increased production of pro-inflammatory cytokines, which were potentially mediated by the extracellular signal-regulated kinase (ERK) and p38 signaling pathways. The results of the present study indicated that macrophages infiltrating injured mucosa express Gpnmb, and that Gpnmb-positive macrophages may ameliorate inflammation in the intestinal mucosa by decreasing pro-inflammatory cytokine production via the ERK and p38 signaling pathways.

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Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats

Cited by 33 publications

References 20 publications

Bioinformatics Multivariate Analysis Determined a Set of Phase-Specific Biomarker Candidates in a Novel Mouse Model for Viral Myocarditis

Bioinformatics Multivariate Analysis Determined a Set of Phase-Specific Biomarker Candidates in a Novel Mouse Model for Viral Myocarditis

Comparison of bone morphogenetic protein‐2 and osteoactivin for mesenchymal cell differentiation: Effects of bolus and continuous administration

Expression of glycoprotein nonmetastatic melanoma protein B in macrophages infiltrating injured mucosa is associated with the severity of experimental colitis in mice

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