The real culprit behind diabetic nephropathy: impaired renal autoregulation?

Liu, Ruisheng

doi:10.14814/phy2.13138

Cited by 3 publications

(3 citation statements)

References 12 publications

(18 reference statements)

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“…The auto-regulatory feedback mechanisms that maintain renal blood flow (RBF) and glomerular filtration rate (GFR) over a wide range of haemodynamic pathophysiological conditions can be disturbed in metabolic and inflammatory disease states promoting the progression of nephropathy [1][2][3]. Measuring and interpreting altered renal perfusion at baseline and in response to physiological stressors would facilitate assessment of individuals at risk of kidney disease or its complications, and assist in the development of pharmacological interventions [4].…”

Section: Introductionmentioning

confidence: 99%

Motion-corrected multiparametric renal arterial spin labelling at 3 T: reproducibility and effect of vasodilator challenge

et al. 2018

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Objectives We investigated the feasibility and reproducibility of free-breathing motion-corrected multiple inversion time (multi-TI) pulsed renal arterial spin labelling (PASL), with general kinetic model parametric mapping, to simultaneously quantify renal perfusion (RBF), bolus arrival time (BAT) and tissue T 1 . Methods In a study approved by the Health Research Authority, 12 healthy volunteers (mean age, 27.6 ± 18.5 years; 5 male) gave informed consent for renal imaging at 3 T using multi-TI ASL and conventional single-TI ASL. Glyceryl trinitrate (GTN) was used as a vasodilator challenge in six subjects. Flow-sensitive alternating inversion recovery (FAIR) preparation was used with background suppression and 3D-GRASE (gradient and spin echo) read-out, and images were motion-corrected. Parametric maps of RBF, BAT and T 1 were derived for both kidneys. Agreement was assessed using Pearson correlation and Bland-Altman plots. Results Inter-study correlation of whole-kidney RBF was good for both single-TI (r 2 = 0.90), and multi-TI ASL (r 2 = 0.92). Single-TI ASL gave a higher estimate of whole-kidney RBF compared to multi-TI ASL (mean bias, 29.3 ml/min/100 g; p <0.001). Using multi-TI ASL, the median T 1 of renal cortex was shorter than that of medulla (799.6 ms vs 807.1 ms, p = 0.01), and mean whole-kidney BAT was 269.7 ± 56.5 ms. GTN had an effect on systolic blood pressure (p < 0.05) but the change in RBF was not significant. Conclusions Free-breathing multi-TI renal ASL is feasible and reproducible at 3 T, providing simultaneous measurement of renal perfusion, haemodynamic parameters and tissue characteristics at baseline and during pharmacological challenge. Key points • Multiple inversion time arterial spin labelling (ASL) of the kidneys is feasible and reproducible at 3 T.• This approach allows simultaneous mapping of renal perfusion, bolus arrival time and tissue T 1 during free breathing.• This technique enables repeated measures of renal haemodynamic characteristics during pharmacological challenge.

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Section: Introductionmentioning

confidence: 99%

Motion-corrected multiparametric renal arterial spin labelling at 3 T: reproducibility and effect of vasodilator challenge

et al. 2018

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“…No evidence of kidney pathology in TRPV2 heterozygous rats. In addition to DR, impaired pressure autoregulation has been proposed to play an important role in the development of diabetic nephropathy (DN) (46). Unlike the retina, however, TRPV4 rather than TRPV2 channels have been proposed as the main mechanosensors that underlie myogenic autoregulation in the kidney (47).…”

Section: Resultsmentioning

confidence: 99%

“…Impaired renal autoregulation has been implicated in the development of diabetic kidney injury ( 46 ). In our study, we observed no obvious renal phenotype in TRPV2 heterozygous rats up to 1 year of age.…”

Section: Discussionmentioning

confidence: 99%

Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats

O’Hare¹,

Esquiva²,

McGahon³

et al. 2022

JCI Insight

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Histone deacetylase inhibitor valproic acid attenuates high glucose‑induced endoplasmic reticulum stress and apoptosis in NRK‑52E cells

Sun

Lin

et al. 2020

Mol Med Rep

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Previous studies have demonstrated that valproic acid (VPa), a histone deacetylase inhibitor, alleviates diabetic nephropathy (dn). However, the biological mechanisms underlying this protective effect remains unclear. This study aimed to investigate the effects of histone deacetylase inhibitor VPa on hyperglycemic induction of nrK-52e cell erS and apoptosis. endoplasmic reticulum stress (erS)-related apoptosis is involved in dn, and improving erS may delay the symptoms of dn. Histone deacetylase regulates gene transcription or expression of erS-related proteins. The present study established an erS model by treating the rat renal tubular epithelial cells nrK-52e with high glucose (HG) and investigated the effects of VPa on the apoptosis of the nrK-52e cells. HG stimulation significantly increased the protein levels of the ERS-related proteins including glucose regulated protein 78 (GrP78), activating transcription factor 4 (aTF4), c/eBP homologous protein (cHoP), caspase-12 and phosphorylated (p)-JnK. VPa treatment further upregulated GrP78 expression and attenuated the levels of aTF4, cHoP, caspase-12 and p-JnK. notably, HG markedly promoted apoptosis of nrK-52e cells by regulating the protein levels of Bax, cleaved caspase-3 and Bcl-2, which was attenuated by simultaneous VPa treatment. Mechanistically, VPa increased the total acetylation levels of histone H4 in nrK-52e cells and increased the histone H4 acetylation of the GrP78 promoter region. in conclusion, VPa attenuated HG-induced erS and apoptosis in nrK-52e cells, which may be due to the regulation of acetylation levels of erS-related proteins. in addition, the present study suggested that Hdacis are promising drugs for treating patients with dn.

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The real culprit behind diabetic nephropathy: impaired renal autoregulation?

Cited by 3 publications

References 12 publications

Motion-corrected multiparametric renal arterial spin labelling at 3 T: reproducibility and effect of vasodilator challenge

Motion-corrected multiparametric renal arterial spin labelling at 3 T: reproducibility and effect of vasodilator challenge

Loss of TRPV2-mediated blood flow autoregulation recapitulates diabetic retinopathy in rats

Histone deacetylase inhibitor valproic acid attenuates high glucose‑induced endoplasmic reticulum stress and apoptosis in NRK‑52E cells

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