Cytokines and the regulation of hypoxia-inducible factor (HIF)-1α

Haddad, John J.; Harb, Hisham L.

doi:10.1016/j.intimp.2004.11.009

Cited by 123 publications

(106 citation statements)

References 181 publications

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“…These recruited cells also produce VEGF, which further promotes angiogenesis and possibly stimulates the proliferation of preadipocytes through paracrine interactions with other cell types (e.g., endothelial cells) (29,40). Expression of HIF-1␣ is consistent with this scenario, though HIF-1␣ expression can be regulated by factors other than hypoxia (45). ROS production is also induced by a variety of environmental cues, including growth factors, making alternative scenarios possible.…”

Section: Discussionmentioning

confidence: 88%

Adipogenesis in Obesity Requires Close Interplay Between Differentiating Adipocytes, Stromal Cells, and Blood Vessels

et al. 2007

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OBJECTIVE-The expansion of adipose tissue mass seen in obesity involves both hyperplasia and hypertrophy of adipocytes. However, little is known about how adipocytes, adipocyte precursors, blood vessels, and stromal cells interact with one another to achieve adipogenesis. RESEARCH DESIGN AND METHODS-We have developed a confocal microscopy-based method of three-dimensional visualization of intact living adipose tissue that enabled us to simultaneously evaluate angiogenesis and adipogenesis in db/db mice.RESULTS-We found that adipocyte differentiation takes place within cell clusters (which we designated adipogenic/angiogenic cell clusters) that contain multiple cell types, including endothelial cells and stromal cells that express CD34 and CD68 and bind lectin. There were close spatial and temporal interrelationships between blood vessel formation and adipogenesis, and the sprouting of new blood vessels from preexisting vasculature was coupled to adipocyte differentiation. CD34 ϩ CD68 ϩ lectin-binding cells could clearly be distinguished from CD34 Ϫ CD68 ϩ macrophages, which were scattered in the stroma and did not bind lectin. Adipogenic/angiogenic cell clusters can morphologically and immunohistochemically be distinguished from crownlike structures frequently seen in the late stages of adipose tissue obesity. Administration of anti-vascular endothelial growth factor (VEGF) antibodies inhibited not only angiogenesis but also the formation of adipogenic/angiogenic cell clusters, indicating that the coupling of adipogenesis and angiogenesis is essential for differentiation of adipocytes in obesity and that VEGF is a key mediator of that process. CONCLUSIONS-Living tissue imaging techniques providenovel evidence of the dynamic interactions between differentiating adipocytes, stromal cells, and angiogenesis in living obese adipose tissue. Diabetes

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Section: Discussionmentioning

confidence: 88%

Adipogenesis in Obesity Requires Close Interplay Between Differentiating Adipocytes, Stromal Cells, and Blood Vessels

et al. 2007

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“…The induction of NF-kB by hypoxia requires the presence of HIF-1a [11], while HIF-1a is activated by pro-inflammatory cytokines such as TNF-a and IL-1b in a NF-kB-dependent manner in several normoxic cell lines, including cancer cells [12][13][14]. Activation of NF-kB leads to TNF-a production, which plays a key role in initiating inflammatory responses, particularly via HIF-1a activation [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and ultrastructural effects of Turkish propolis in a rat model of endotoxin-induced uveitis

Ertürküner

Saraç

Göçmez

et al. 2015

Folia Histochem Cytobiol.

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Introduction. Experimental animal models of acute uveitis, an inflammatory eye disease, can be established via endotoxin-induced inflammation. Propolis, a natural substance collected by honeybees from buds and tree exudates, has antioxidant, antibacterial, antiviral, and anti-inflammatory effects. We investigated the effects of propolis, obtained from the Sakarya province of Turkey, on endotoxin-induced uveitis using immunohistochemical, ultrastructural, and biochemical approaches. Material and methods. Male Wistar albino rats (n = 6/group) received intraperitoneal (ip) lipopolysaccharide (LPS) endotoxin (150 µg/kg) followed by aqueous extract of propolis (50 mg/kg ip) or vehicle; two additional groups received either saline (control) or propolis only. After 24 h, aqueous humor (AH) was collected from both eyes of each animal for analysis of tumor necrosis factor-a (TNF-a) and hypoxia-inducible factor-1a (HIF-1a). Right eyeballs were paraffin-embedded for immunohistochemical staining of nuclear factor kB (NF-kB)/p65 and left eyeballs were araldite-embedded for ultrastructural analysis. Results. Treatment of LPS-induced uveitis with propolis significantly reduced ciliary body NF-kB/p65 immunoreactivity and AH levels of HIF-1a and TNF-a. Ultrastructural analysis showed fewer vacuoles and reduced mitochondrial degeneration in the retinal pigment epithelium, as compared to the uveitis group. The intercellular spaces of the inner nuclear layer and outer limiting membrane were comparable with those of the control group; no polymorphonuclear cells or stasis was observed in intravascular or extravascular spaces. Conclusions. This is the first report demonstrating an anti-inflammatory effect of Turkish propolis in a rat model of LPS-induced acute uveitis, suggesting a therapeutic potential of propolis for the treatment of inflammatory ophthalmic diseases.

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“…The regulation of growth factors and hormones, such as transform growth factor beta (TGF-β), fibroblast growth factor (FGF), insulin-like growth factor 1 (IGF-1), bone morphogenetic protein (BMP) and parathormone (PTH), on MSCs proliferation and differentiation have been studied thoroughly (Haddad and Harb 2005;Qi et al 2009;Huang et al 2010). It has been reported that MSCs cultured in vitro would differentiate into osteoblasts spontaneously (Seong et al 2010;Mikami et al 2011).…”

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confidence: 99%

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Huang

Deng

Wang

et al. 2011

Tohoku J. Exp. Med.

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Mesenchymal stem sells (MSCs) have received much attention in the field of bone tissue engineering due to their biological capability to differentiate into osteogenic lineage cells. Hypoxia-inducible factor 1alpha (HIF-1α) plays an important role in the MSC-related bone regeneration during hypoxia, while core binding factor alpha 1 (Cbfα1) is a transcription regulator that is involved in the chondrocyte differentiation and ossification. In the present study, we investigated the effects of hypoxia on biological capability of MSCs. MSCs were isolated from adult rabbit bone marrow, and were cultured in vitro under normoxia (air with 5% CO 2 ) or hypoxia (5% CO 2 and 95% N 2 ). The proliferation of MSCs, alkaline phosphatase (ALP) activity, and production of collagens type I and type III (Col I/III) were examined. The expression levels of HIF-1α and Cbfα1 were measured by real-time PCR and western blot analyses. We found that hypoxia significantly induced the proliferation of MSCs and increased ALP activity and the production of Col I/III. Moreover, hypoxia increased the expression of Cbfα1 mRNA after 12 h, whereas the expression of HIF-1α mRNA was increased after 1 h of hypoxia. Knockdown of HIF-1α expression with a small interfering RNA significantly increased the expression levels of Cbfα1 protein either under the normoxia or hypoxia condition. Our results indicate that hypoxia enhances MSCs to differentiate into osteogenic lineage cells and suggest that Cbfα1 may be negatively regulated by HIF-1α.

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Cytokines and the regulation of hypoxia-inducible factor (HIF)-1α

Cited by 123 publications

References 181 publications

Adipogenesis in Obesity Requires Close Interplay Between Differentiating Adipocytes, Stromal Cells, and Blood Vessels

Adipogenesis in Obesity Requires Close Interplay Between Differentiating Adipocytes, Stromal Cells, and Blood Vessels

Anti-inflammatory and ultrastructural effects of Turkish propolis in a rat model of endotoxin-induced uveitis

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

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