Altered wound healing in mice lacking a functional osteopontin gene (spp1).

Liaw, Lucy; Birk, David E.; Ballas, Christopher B.; Whitsitt, Jeffrey S.; Davidson, Jeffrey M.; Hogan, Brigid L.M.

doi:10.1172/jci2131

Cited by 607 publications

(303 citation statements)

References 45 publications

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“…It has been demonstrated that OPN-deficient mice exhibit reduced levels of collagen in the heart after myocardial infarction [22]and in the kidney after ureteral ligation [23]. Furthermore, collagen fiber diameter has been found to be reduced in OPN-deficient mice after skin incision [24]. …”

Section: Discussionmentioning

confidence: 99%

Altered Vascular Remodeling in Osteopontin-Deficient Atherosclerotic Mice

et al. 2004

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Background: Osteopontin (OPN) is a cell-binding phosphoprotein with proposed functions in atherosclerosis. The aim of this study was to examine how OPN deficiency affects the atherosclerotic process. Methods: ApoE/LDL receptor/OPN triple knockout (ALO) mice were generated by crossing OPN null mice with ApoE/LDL receptor-deficient (AL) mice. Analysis were made on tissue sections from the aortic arch of 8-, 20- and 34-week female AL and ALO mice and included morphometric measurements, collagen staining, TUNEL staining and immunohistochemistry with antibodies to OPN, macrophages and proliferating cellular nuclear antigen (PCNA). Results: Lesion and media areas were significantly smaller and collagen accumulation in lesions was significantly reduced in 34-week-old ALO mice compared with AL mice. The numbers of proliferating and apoptotic cells were increased in lesions of 34 weeks old ALO mice. Furthermore, the plasma levels of SAA and total cholesterol were significantly decreased in 34 weeks old ALO mice. Conclusions: The present study shows that OPN deficiency reduces atherogenesis in atherosclerotic mice. The results corroborate and extend recently published findings and also include novel data on the role of OPN in the process of remodeling, inflammation and lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

Altered Vascular Remodeling in Osteopontin-Deficient Atherosclerotic Mice

et al. 2004

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“…S1C. 9 Immunoblotting of whole lung protein extracts from Spp1 C/C and Spp1 ¡/¡ mice and from HEK293T human embryonic kidney cells, known to produce iSPP1 and sSPP1, 25 revealed predominant expression of processed sSPP1 in the lungs (Fig. S1D).…”

Section: Host Osteopontin Expression and Its Impact On Lung Metastasismentioning

confidence: 97%

“…5 Osteopontin (also known as secreted phosphoprotein 1, SPP1), an adhesive glycophosphoprotein widely expressed in tissues, body fluids, and cells under normal conditions, regulates physiologic processes such as development, differentiation, inflammation, and wound healing. [6][7][8][9] In addition, SPP1 is highly expressed in the microenvironment of various tumors, both by malignant and host cells. [10][11][12] Osteopontin has been linked with enhanced tumor progression and metastasis by modulating cell-cell interactions, by activating signal transduction pathways, by altering gene expression, and by promoting tumor cell survival.…”

Section: Introductionmentioning

confidence: 99%

Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis

et al. 2016

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The lungs are ubiquitous receptacles of metastases originating from various bodily tumors. Although osteopontin (SPP1) has been associated with tumor dissemination, the role of its isoforms in lung-directed metastasis is incompletely understood. We employed syngeneic mouse models of spontaneous and induced lung-targeted metastasis in C57BL/6 mice competent and deficient in both Spp1 alleles. Tumorderived osteopontin expression was modulated using either stable anti-Spp1 RNA interference, or forced overexpression of intracellular and secreted Spp1 isoforms. Identified osteopontin's downstream partners were validated using lung adenocarcinoma cells conditionally lacking the Trp53 gene and Ccr2-deficient mice. We determined that host-derived osteopontin was dispensable for pulmonary colonization by different tumor types. Oppositely, tumor-originated intracellular osteopontin promoted tumor cell survival by preventing tumor-related protein 53-mediated apoptosis, while the secretory osteopontin functioned in a paracrine mode to accelerate lung metastasis by enhancing tumor-derived C-C-motif chemokine ligand 2 signaling to cognate host receptors. As new ways to target osteopontin signaling are becoming available, the cytokine may constitute an important therapeutic target against pulmonary involvement by cancers of other organs. KEYWORDSC-C-motif chemokine ligand 2; inflammation and cancer; secreted phosphoprotein 1; spontaneous lung metastasis; tumor-related protein 53

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“…Recently, a critical role of OPN in fibrosis in several organs has been reported [12,13,14,15]. Several studies have speculated that OPN may also play a role in glomerular fibrosis [20,22,23].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, involvement of OPN in fibrosis in several organs has been demonstrated [12,13,14]. The OPN mutant mice showed a greater disorganization of matrix in their skin incisions [15]. OPN is required for differentiation of myofibroblasts, a major player in fibrosis [16].…”

Section: Introductionmentioning

confidence: 99%

Osteopontin Overproduction Is Associated with Progression of Glomerular Fibrosis in a Rat Model of Anti-Glomerular Basement Membrane Glomerulonephritis

Merszei

Torres

et al. 2010

Am J Nephrol

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Background: Glomerular fibrosis is the common end result of glomerulonephritis (GN) regardless of etiology. In our rat model for anti-glomerular basement membrane GN, severe fibrosis follows glomerular inflammation. We investigated the association between expression of extracellular matrix (ECM) proteins and progression of glomerular fibrosis. Methods: Expression of ECM genes in glomeruli was determined at RNA and protein levels. Immunofluorescence was applied to identify cell sources for the molecules. Results: DNA microarray for ECM genes, quantitative RT-PCR and Western blot revealed significant upregulation of osteopontin (OPN), a multifunctional molecule, in the glomeruli only after onset of glomerular fibrosis. Two-dimensional electrophoresis showed that the expressed OPN was in three major isoforms. Immunofluorescence showed that fibrotic tissues in glomeruli accumulated massive deposits of extracellular OPN. Both in vivo and in vitro experiments showed that a novel population of multinucleated α-smooth muscle actin⁺CD90^– myofibroblast-like cells, which surrounded fibrotic tissue, was the main source of OPN during progression of fibrosis. Since senescence-associated β-galactosidase activity was detected in those cells both in vitro and in vivo, these cells probably were terminally differentiated senescent myofibroblasts. Conclusion: OPN has been implicated in fibrosis in several organs. Our results suggest potential roles of OPN and its main source, the senescent myofibroblasts, in glomerular fibrosis.

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Altered wound healing in mice lacking a functional osteopontin gene (spp1).

Cited by 607 publications

References 45 publications

Altered Vascular Remodeling in Osteopontin-Deficient Atherosclerotic Mice

Altered Vascular Remodeling in Osteopontin-Deficient Atherosclerotic Mice

Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis

Osteopontin Overproduction Is Associated with Progression of Glomerular Fibrosis in a Rat Model of Anti-Glomerular Basement Membrane Glomerulonephritis

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