The role of hypoxia and Morg1 in renal injury

Loeffler, Ivonne; Wolf, Günter

doi:10.1111/eci.12405

Cited by 16 publications

(13 citation statements)

References 93 publications

(221 reference statements)

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“…Additionally, several studies in CKD animal models suggest that HIF-1α is suppressed by factors including oxidative stress and uremia and underlies the pathogenesis of CKD18. HIF-1α has been extensively described as a key factor for cell adaptation to hypoxia, including renal tissue19. Consistently with our previous results3 and the findings presented here, the activation of HIF-1α post-ischemia by pharmacological treatment with PHDs inhibitors significantly reduces renal I/R injury20.…”

Section: Discussionsupporting

confidence: 90%

HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p

Conde

Giménez-Moyano

Martín-Gómez

et al. 2017

Sci Rep

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Ischemia/reperfusion (I/R) leads to Acute Kidney Injury. HIF-1α is a key factor during organ response to I/R. We previously demonstrated that HIF-1α is induced during renal reperfusion, after ischemia. Here we investigate the role of HIF-1α and the HIF-1α dependent mechanisms in renal repair after ischemia. By interference of HIF-1α in a rat model of renal I/R, we observed loss of expression and mis-localization of e-cadherin and induction of α-SMA, MMP-13, TGFβ, and collagen I. Moreover, we demonstrate that HIF-1α inhibition promotes renal cell infiltrates by inducing IL-1β, TNF-α, MCP-1 and VCAM-1, through NFkB activity. In addition, HIF-1α inhibition induced proximal tubule cells proliferation but it did not induce compensatory apoptosis, both in vivo. In vitro, HIF-1α knockdown in HK2 cells subjected to hypoxia/reoxygenation (H/R) promote cell entry into S phase, correlating with in vivo data. HIF-1α interference leads to downregulation of miR-127-3p and induction of its target gene Bcl6 in vivo. Moreover, modulation of miR-127-3p in HK2 cells subjected to H/R results in EMT regulation: miR127-3p inhibition promote loss of e-cadherin and induction of α-SMA and collagen I. In conclusion, HIF-1α induction during reperfusion is a protector mechanism implicated in a normal renal tissue repair after I/R.

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Section: Discussionsupporting

confidence: 90%

HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p

Conde

Giménez-Moyano

Martín-Gómez

et al. 2017

Sci Rep

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“…It has been shown that HIF, as a transcription factor, plays a critical role in regulating transcription of genes that promote angiogenesis, erythropoiesis, cell metabolism, cell survival and apoptosis . HIF is central to real protection in different models of kidney injury like chronic kidney disease, renal ischaemia‐reperfusion injury and nephrotoxic or ischaemic acute kidney injury . In previous studies, suppression of HIF at different levels of regulation was observed in renal cells induced by cisplatin and HIF activation attenuated apoptosis .…”

Section: Discussionsupporting

confidence: 79%

Oral deferiprone administration ameliorates cisplatin-induced nephrotoxicity in rats

Makhdoumi

Abnous

Mehri

et al. 2018

Journal of Pharmacy and Pharmacology

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“…A wide range of pathogenesis including ischemia, hypertension, and infections could result in AKI [2], among which ischemia is known as a main leading insult that causes dysfunction of kidney [3]. Some studies reported that AKI could increase the risk of chronic kidney disease (CKD) development and end-stage renal disease (ESRD) with time.…”

Section: Introductionmentioning

confidence: 99%

7,8-DHF Treatment Induces Cyr61 Expression to Suppress Hypoxia Induced ER Stress in HK-2 Cells

Zhang

Liu

et al. 2016

BioMed Research International

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Acute kidney injury (AKI) is a common syndrome which is strongly linked to high morbidity and mortality. Hypoxia is the leading cause of AKI and the proximal renal tubular cells are the most damaged part in the kidney during this period. It has been observed that 7,8-dihydroxyflavone (7,8-DHF) plays a protective role by acting on antiapoptosis and antioxidative stress. In this study we explored functions of 7,8-DHF in protecting human proximal tubular cell line HK-2 from hypoxia insults. We observed that treatment of 7,8-DHF could improve the viability of ischemic cell. Mechanistically, we found that 7,8-DHF could elevate the expression of cysteine-rich protein 61 (Cyr61), a protective immediate early gene in AKI. In addition, treatment of 7,8-DHF decreased CCAAT/enhancer-binding protein homologous protein (CHOP) expression, which is a marker protein during endoplasmic reticulum (ER) stress activation. Intriguingly, overexpression of Cyr61 significantly reduced CHOP expression. Taken together, our results provide novel insights into the possible protective role of 7,8-DHF by activating Cyr61 signaling and suppressing ER stress in hypoxic HK-2 cells which have potential clinical implications for the treatment of AKI.

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The role of hypoxia and Morg1 in renal injury

Cited by 16 publications

References 93 publications

HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p

HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p

Oral deferiprone administration ameliorates cisplatin-induced nephrotoxicity in rats

7,8-DHF Treatment Induces Cyr61 Expression to Suppress Hypoxia Induced ER Stress in HK-2 Cells

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