Transforming Growth Factor-β
            <sub>1</sub>
            Modulates Oxidatively Modified LDL–Induced Expression of Adhesion Molecules

Chen, Hongjiang; Li, Dayuan; Saldeen, Tom; Mehta, Jawahar L.

doi:10.1161/hh2401.100598

Cited by 60 publications

(36 citation statements)

References 52 publications

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“…However, interestingly, our results showed a significant correlation between the tubulointerstitial mRNA expression for LOX-1 mRNA and extent of proteinuria (Fig. 4) (22)(23)(24). More recent studies have also reported relationships between high-glucose, Ox-LDL and albuminuria (25,26 …”

Section: Detection Of Lox-1 Mrna By In Situ Hybridizationsupporting

confidence: 63%

Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in the Tubulointerstitial Area Likely Plays an Important Role in Human Diabetic Nephropathy

et al. 2009

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Section: Detection Of Lox-1 Mrna By In Situ Hybridizationsupporting

confidence: 63%

Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in the Tubulointerstitial Area Likely Plays an Important Role in Human Diabetic Nephropathy

et al. 2009

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“…We used TGF␤ 1 ACT to up-regulate TGF␤ 1 because previous studies (5,14) have shown that the active moiety of TGF␤ 1 results in significantly greater biological effects than the latent form of TGF␤ 1 ACT . The suggestion of a role of LOX-1 in the biological effects of TGF␤ 1 comes from studies that indicate that TGF␤ 1 influences the pro-inflammatory effect of oxidized low density lipoprotein (12). In these studies, pretreatment of endothelial cells with anti-LOX-1 antibody attenuated the synthesis of TGF␤ 1 in response to oxidized low density lipoprotein.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that TGF␤ 1 can regulate LOX-1 expression in vascular endothelial cells, smooth muscle cells, and monocytes/macrophages (10,11). Another study showed that LOX-1 blockade reduces TGF␤ 1 protein expression in endothelial cells (12). The present study was conducted to examine whether and how LOX-1 mediates TGF␤ 1 -mediated collagen production.…”

mentioning

confidence: 96%

Regulation of TGFβ1-mediated Collagen Formation by LOX-1

Dandapat

Sun

et al. 2008

Journal of Biological Chemistry

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Transforming growth factor ␤ 1 (TGF␤ 1 ) activation leads to tissue fibrosis. Here, we report on the role of LOX-1, a lectin-like 52-kDa receptor for oxidized low density lipoprotein, in TGF␤ 1 -mediated collagen expression and underlying signaling in mouse cardiac fibroblasts. TGF␤ 1 was overexpressed in wildtype (WT) and LOX-1 knock-out mouse cardiac fibroblasts by transfection with adeno-associated virus type 2 vector carrying the active TGF␤ 1 moiety (AAV/TGF␤ 1 ACT ). Transfection of WT mouse cardiac fibroblasts with AAV/TGF␤ 1 ACT markedly enhanced the expression of NADPH oxidases (p22 phox , p47 phox , and gp91 phox subunits) and LOX-1, formation of reactive oxygen species, and collagen synthesis, concomitant with an increase in the activation of p38 and p44/42 mitogen-activated protein kinases (MAPK). The TGF␤ 1 -mediated increase in collagen synthesis was markedly attenuated in the LOX-1 knock-out mouse cardiac fibroblasts as well as in WT mouse cardiac fibroblasts treated with a specific anti-LOX-1 antibody. Treatment with anti-LOX-1 antibody also reduced NADPH oxidase expression and MAPK activation. The NADPH oxidase inhibitors and gp91phox small interfering RNA reduced LOX-1 expression, MAPK activation, and collagen formation. The p38 MAPK inhibitors as well as the p44/42 MAPK inhibitors reduced collagen formation without affecting LOX-1 expression in cardiac fibroblasts. These observations suggest that collagen synthesis in cardiac fibroblasts involves a facilitative interaction between TGF␤ 1 -NADPH oxidase and LOX-1. Further, the activation of MAPK pathway appears to be downstream of TGF␤ 1 -reactive oxygen species-LOX-1 cascade.Cardiac fibrosis, characterized by accumulation of matrix proteins in the extracellular space in the perivascular region, is closely associated with the development of heart failure. Among the extracellular matrix proteins, up to 85% are collagens, of which type 1 (collagen I) and type 3 (collagen III) constitute two-thirds of total collagens in most tissues (1). Transforming growth factor (TGF) 3 ␤ 1 is one of the most pleiotropic and multifunctional peptides known (2). It exerts potent effects on many different cell types and is involved in a wide variety of biological processes (2). The cellular actions of TGF␤ 1 are dependent not only on the cell type but also on its state of differentiation and the cytokine milieu (3). Although there is evidence that TGF␤ 1 stimulates fibroblast growth, enhances collagen synthesis, and suppresses collagen degradation (2) ACT that appears to be functionally relevant in the process of ischemia-reperfusion (5).LOX-1 is a lectin-like receptor for oxidized low density lipoprotein (6). It is also up-regulated in response to oxidative stress (7). Activation of LOX-1 enhances the growth of cardiac fibroblasts and promotes collagen synthesis (8, 9). It has been reported that TGF␤ 1 can regulate LOX-1 expression in vascular endothelial cells, smooth muscle cells, and monocytes/macrophages (10, 11). Another study showed that LOX-1 blockade reduc...

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“…Oxidized LDL, for example, is scavenged through LOX-1 (94), which is highly expressed in blood vessels in hypertension, diabetes, and dyslipidemia (95). Oxidized LDL uptake by LOX-1 triggers a variety of actions: It reduces eNOS expression (96) and further stimulates adhesion molecule expression (97). LOX-1 expression can be stimulated by Ang II and endothelin-1 (98,99).…”

Section: Pathophysiologic Effects Of Endothelial Dysfunctionmentioning

confidence: 99%

Endothelial Dysfunction

Endemann¹

2004

Journal of the American Society of Nephrology

1,112

834

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Abstract. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory state, and prothrombic properties. It is associated with most forms of cardiovascular disease, such as hypertension, coronary artery disease, chronic heart failure, peripheral artery disease, diabetes, and chronic renal failure. Mechanisms that participate in the reduced vasodilatory responses in endothelial dysfunction include reduced nitric oxide generation, oxidative excess, and reduced production of hyperpolarizing factor. Upregulation of adhesion molecules, generation of chemokines such as macrophage chemoattractant peptide-1, and production of plasminogen activator inhibitor-1 participate in the inflammatory response and contribute to a prothrombic state. Vasoactive peptides such as angiotensin II and endothelin-1; the accumulation of asymmetric dimethylarginine, an endogenous nitric oxide inhibitor; hypercholesterolemia; hyperhomocysteinemia; altered insulin signaling; and hyperglycemia can contribute to these different mechanisms. Detachment and apoptosis of endothelial cells (anoikis) are associated phenomena. Endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Reductions in circulating endothelial progenitor cells that participate in regeneration of the endothelium participate in endothelial pathophysiology. The severity of endothelial dysfunction has been shown to have prognostic value for cardiovascular events.

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Transforming Growth Factor-β ₁ Modulates Oxidatively Modified LDL–Induced Expression of Adhesion Molecules

Cited by 60 publications

References 52 publications

Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in the Tubulointerstitial Area Likely Plays an Important Role in Human Diabetic Nephropathy

Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in the Tubulointerstitial Area Likely Plays an Important Role in Human Diabetic Nephropathy

Regulation of TGFβ1-mediated Collagen Formation by LOX-1

Endothelial Dysfunction

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Transforming Growth Factor-β 1 Modulates Oxidatively Modified LDL–Induced Expression of Adhesion Molecules

Cited by 60 publications

References 52 publications

Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in the Tubulointerstitial Area Likely Plays an Important Role in Human Diabetic Nephropathy

Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in the Tubulointerstitial Area Likely Plays an Important Role in Human Diabetic Nephropathy

Regulation of TGFβ1-mediated Collagen Formation by LOX-1

Endothelial Dysfunction

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Transforming Growth Factor-β ₁ Modulates Oxidatively Modified LDL–Induced Expression of Adhesion Molecules