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

Yamamoto, Naoyuki; Toyoda, Masao; Abe, Makiko; Kobayashi, Takako; Kobayashi, Kazuo; Kato, Mayuko; Miyauchi, Masaaki; Kimura, Moritsugu; Umezono, Tomoya; Suzuki, Daisuke

doi:10.2169/internalmedicine.48.1251

Cited by 26 publications

(22 citation statements)

References 26 publications

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“…This was also noted to be the pathway by which OxLDL activation of AngII=R leads to Smad activation. TGF-b, angiotensin II (Ang II), and ischemia can upregulate tubulointerstitial LOX-1 expression, further enhancing deleterious effects of OxLDL on tubulointerstitum ultimately leading to fibrosis (307).…”

Section: Oxldl In Diabetes Mellitusmentioning

confidence: 99%

Oxidized LDL: Diversity, Patterns of Recognition, and Pathophysiology

Levitan

Volkov

Subbaiah

2010

Antioxidants & Redox Signaling

366

328

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Oxidative modification of LDL is known to elicit an array of pro-atherogenic responses, but it is generally underappreciated that oxidized LDL (OxLDL) exists in multiple forms, characterized by different degrees of oxidation and different mixtures of bioactive components. The variable effects of OxLDL reported in the literature can be attributed in large part to the heterogeneous nature of the preparations employed. In this review, we first describe the various subclasses and molecular composition of OxLDL, including the variety of minimally modified LDL preparations. We then describe multiple receptors that recognize various species of OxLDL and discuss the mechanisms responsible for the recognition by specific receptors. Furthermore, we discuss the contentious issues such as the nature of OxLDL in vivo and the physiological oxidizing agents, whether oxidation of LDL is a prerequisite for atherogenesis, whether OxLDL is the major source of lipids in foam cells, whether in some cases it actually induces cholesterol depletion, and finally the Janus-like nature of OxLDL in having both pro-and anti-inflammatory effects. Lastly, we extend our review to discuss the role of LDL oxidation in diseases other than atherosclerosis, including diabetes mellitus, and several autoimmune diseases, such as lupus erythematosus, anti-phospholipid syndrome, and rheumatoid arthritis. Antioxid. Redox Signal. 13, 39-75.

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Section: Oxldl In Diabetes Mellitusmentioning

confidence: 99%

Oxidized LDL: Diversity, Patterns of Recognition, and Pathophysiology

Levitan

Volkov

Subbaiah

2010

Antioxidants & Redox Signaling

366

328

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“…The OLR-1 up-regulation in the kidney of Dahl salt-sensitive rats was parallel to glomerulosclerotic changes and renal dysfunction, suggesting a possible pathogenetic role for renal OLR-1 in the progression to hypertensive glomerulosclerosis (Nagase et al, 2000). In subjects with diabetic mellitus, increased expression of OLR-1 mRNA in the tubulointerstitial area may be closely linked to the development and progression of diabetic nephropathy and tubulointerstitial damage (Yamamoto et al 2009). The role of OLR-1 in the development of angiotensin II-induced hypertension and subsequent renal damage was recently reported (Hu et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

G501C polymorphism of the oxidized LDL receptor gene is associated with albuminuria in Chinese essential hypertension patients

Hou¹,

Hu²,

Cui³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. Albuminuria is an independent predictor of renal and cardiovascular complications in hypertensive subjects. We previously showed that lectin-like oxidized low-density lipoprotein receptor 1 (OLR-1) polymorphisms at G501C are associated with susceptibility to essential hypertension and serum C-reactive protein levels. We have now investigated a possible association between OLR-1 polymorphisms at G501C, genotyped by PCR-RFLP, and severity of albuminuria in 307 hypertensive Chinese subjects and 225 age-and gender-matched controls. Urine albumin concentration/urine creatinine concentrations (ACR) were measured to evaluate the severity of albuminuria. Hypertensive subjects had a significantly higher frequency of the CC genotype and the C allele of the OLR-1 polymorphism than controls; this was also true for hypertensive subjects with macroalbuminuria and microalbuminuria OLR-1 polymorphism at G501C in essential hypertension patients compared to those with normoalbuminuria. The mean ACR levels and mean serum C-reactive protein levels in CC carriers were significantly higher than in GG and GC carriers. There was a significant, positive correlation between serum hs-C-reactive protein levels and ACR levels. We conclude that OLR-1 polymorphisms at G501C affect the severity of albuminuria in essential hypertension patients.

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“…Diabetic nephropathy (DN) is a common cause of endstage renal disease [1] . Tubular dysfunction has been reported in patients with diabetes mellitus in the absence of microalbuminuria, suggesting a pivotal role of tubulo-interstitium in the development of DN [2] .…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating evidence indicates that LOX-1 plays an important role in the pathogenesis and progression of DN [1,5] . It has been reported that LOX-1 is strongly expressed in the kidneys of obese diabetic rats, and its expression parallels renal dysfunction [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

High Glucose Enhances oxLDL-Induced Apoptosis in Human Renal Proximal Tubular Epithelial Cells Largely via Inducing Lectin-Like ox-LDL Receptor-1

Zhou

Liu²,

Duan³

et al. 2016

Pharmacology

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Background: High blood glucose is characteristic of diabetic nephropathy (DN). Both lectin-like ox-LDL receptor-1 (LOX-1) and renal tubular epithelial cells apoptosis reportedly are important for the pathogenesis and progression of DN. In this study, we explored the regulatory effects of high glucose on the expression of LOX-1 and its impact on oxLDL-induced apoptosis in human renal proximal tubular epithelial cells (HRPTEpCs). Methods: Primary HRPTEpCs were treated with high glucose with or without concurrent treatment with selective p38 mitogen-activated protein kinase (MAPK) inhibitor PD169316 or lentiviral knockdown of LOX-1. HRPTEpCs cultured in normal glucose concentration (5.5 mmol/l) was used as a control. Results and Conclusion: High glucose concentration dependency increased the expression of LOX-1, which led to increased ox-LDL binding in HRPTEpCs. In addition, high glucose upregulated the LOX-1 gene promoter activity but not its mRNA stability in HRPTEpCs; the effect was abolished by PD169316. Furthermore, high glucose markedly enhanced oxLDL-induced apoptosis in HRPTEpCs, which was largely abolished by knockdown of LOX-1. This study demonstrates that high glucose induces the expression of LOX-1 at the gene promoter/transcription level mainly by a p38 MAPK-dependent mechanism, which enhances oxLDL-induced apoptosis in renal tubular epithelial cells. It adds new insights into the molecular mechanisms underlying DN.

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

Abstract: Objective Diabetic nephropathy (DN) is a common cause of end

Cited by 26 publications

References 26 publications

Oxidized LDL: Diversity, Patterns of Recognition, and Pathophysiology

Oxidized LDL: Diversity, Patterns of Recognition, and Pathophysiology

G501C polymorphism of the oxidized LDL receptor gene is associated with albuminuria in Chinese essential hypertension patients

High Glucose Enhances oxLDL-Induced Apoptosis in Human Renal Proximal Tubular Epithelial Cells Largely via Inducing Lectin-Like ox-LDL Receptor-1

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