Inhibition of prolyl hydroxylase domain-containing protein on hypertension/renal injury induced by high salt diet and nitric oxide withdrawal

Dallatu, Mohammad K.; Choi, Myung Seoup; Oyekan, Adebayo

doi:10.1097/hjh.0b013e32836356a0

Cited by 12 publications

(13 citation statements)

References 30 publications

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“…Moreover, genetic ablation of renal epithelial Hif-1α inhibits the development of renal tubulointerstitial fibrosis in unilateral ureteral obstruction rats and that over-expression of HIF-1α in tubular epithelial cells promotes interstitial fibrosis in 5/6 nephrectomy mice 39 . In contrast, increasing HIF-1α levels exacerbates kidney damage in a rat model of hypertension induced by high salt diet and nitric oxide withdrawal 40 . Taken together, these studies suggest that overproduction of HIF-1α in the epithelial cells of the renal tubule interstitium contributes to kidney disease by stimulating EMT and fibrosis.…”

Section: Discussionmentioning

confidence: 97%

Elevated Endothelial Hypoxia-Inducible Factor-1α Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease

et al. 2015

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Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1alpha is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with RT-PCR profiling revealed that elevated endothelial HIF-1α is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1α gene expression was induced by Ang II in a nuclear factor-κB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1α and Nf-κb genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1α gene expression in endothelial cells is detrimental to induce kidney injury, hypertension and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease.

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Section: Discussionmentioning

confidence: 97%

Elevated Endothelial Hypoxia-Inducible Factor-1α Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease

et al. 2015

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“…Cobalt chloride also inhibited tubulointerstitial injury in Thy1 nephropathy . There is also some evidence that HIF activation can blunt progression from AKI to CKD, as reviewed by Tanaka et al However, in a model of hypertension and CKD induced by blockade of nitric oxide synthase and a high salt diet, the PHD inhibitor dimethyloxallyl glycine exacerbated hypertension and urinary protein excretion …”

Section: Does Tissue Hypoxia Drive Signalling Cascades That Lead To Tmentioning

confidence: 97%

Renal hypoxia in kidney disease: Cause or consequence?

et al. 2017

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Tissue hypoxia has been proposed as an important factor in the pathophysiology of both chronic kidney disease (CKD) and acute kidney injury (AKI), initiating and propagating a vicious cycle of tubular injury, vascular rarefaction, and fibrosis and thus exacerbation of hypoxia. Here, we critically evaluate this proposition by systematically reviewing the literature relevant to the following six questions: (i) Is kidney disease always associated with tissue hypoxia? (ii) Does tissue hypoxia drive signalling cascades that lead to tissue damage and dysfunction? (iii) Does tissue hypoxia per se lead to kidney disease? (iv) Does tissue hypoxia precede pathology? (v) Does tissue hypoxia colocalize with pathology? (vi) Does prevention of tissue hypoxia prevent kidney disease? We conclude that tissue hypoxia is a common feature of both AKI and CKD. Furthermore, at least under in vitro conditions, renal tissue hypoxia drives signalling cascades that lead to tissue damage and dysfunction. Tissue hypoxia itself can lead to renal pathology, independent of other known risk factors for kidney disease. There is also some evidence that tissue hypoxia precedes renal pathology, at least in some forms of kidney disease. However, we have made relatively little progress in determining the spatial relationships between tissue hypoxia and pathological processes (i.e. colocalization) or whether therapies targeted to reduce tissue hypoxia can prevent or delay the progression of renal disease. Thus, the hypothesis that tissue hypoxia is a "common pathway" to both AKI and CKD still remains to be adequately tested.

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“…In human CKD, there is an association of renal HIF-1α expression and tubulointerstitial injury [45]. Consistently, elevated epithelial HIF-1α levels exacerbate the progression of kidney damage and renal fibrosis in a rat model of hypertension induced by high-salt diet and nitric oxide withdrawal [47]. Altogether, this evidence implies that activation of HIF-1α signaling in renal epithelial cells may accelerate fibrogenesis in CKD.…”

Section: Hif In Chronic Kidney Disease (Ckd)-associated Renal Fibrmentioning

confidence: 97%

“…Chronic hypoxia has long been considered to be the final common pathological condition for various types of CKDs. Accumulating evidence show that HIF, especially HIF-1α, is a key regulator of renal fibrosis under various pathological conditions [39,40,41,42,43,44,45,46,47,48,49,50,51,52]. However, it is still controversial whether HIF is pro-fibrotic or anti-fibrotic.…”

Section: Hif In Chronic Kidney Disease (Ckd)-associated Renal Fibrmentioning

confidence: 99%

Hypoxia, HIF, and Associated Signaling Networks in Chronic Kidney Disease

Liu¹,

Wei²,

Guo³

et al. 2017

IJMS

107

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The pathogenesis of chronic kidney disease (CKD) is complex and apparently multifactorial. Hypoxia or decrease in oxygen supply in kidney tissues has been implicated in CKD. Hypoxia inducible factors (HIF) are a small family of transcription factors that are mainly responsive to hypoxia and mediate hypoxic response. HIF plays a critical role in renal fibrosis during CKD through the modulation of gene transcription, crosstalk with multiple signaling pathways, epithelial-mesenchymal transition, and epigenetic regulation. Moreover, HIF also contributes to the development of various pathological conditions associated with CKD, such as anemia, inflammation, aberrant angiogenesis, and vascular calcification. Treatments targeting HIF and related signaling pathways for CKD therapy are being developed with promising clinical benefits, especially for anemia. This review presents an updated analysis of hypoxia response, HIF, and their associated signaling network involved in the pathogenesis of CKD.

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Inhibition of prolyl hydroxylase domain-containing protein on hypertension/renal injury induced by high salt diet and nitric oxide withdrawal

Cited by 12 publications

References 30 publications

Elevated Endothelial Hypoxia-Inducible Factor-1α Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease

Elevated Endothelial Hypoxia-Inducible Factor-1α Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease

Renal hypoxia in kidney disease: Cause or consequence?

Hypoxia, HIF, and Associated Signaling Networks in Chronic Kidney Disease

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