High Glucose Up-regulates ADAM17 through HIF-1α in Mesangial Cells

Li, Renzhong; Uttarwar, Lalita; Gao, Bo; Charbonneau, Martine; Shi, Yixuan; Chan, John S.D.; Dubois, Claire M.; Krepinsky, Joan C.

doi:10.1074/jbc.m115.651604

Cited by 63 publications

(52 citation statements)

References 53 publications

(85 reference statements)

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“…Various studies on TFs involved in the upregulation of ADAM17 have shown that under specific conditions, such as hypoxia, ADAM17 expression is upregulated by different TFs565758. In this study, we found that CUX1 was the only TF conserved in both mouse and human predicted to bind to ADAM17 .…”

Section: Discussionmentioning

confidence: 51%

Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

et al. 2016

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Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours upregulates the expression of ADAM17, thereby activating NOTCH signalling. Using prostate conditional inactivation of both Pten and Notch1 along with preclinical trials carried out in Pten-null prostate conditional mouse models, we demonstrate that Pten-deficient prostate tumours are addicted to the NOTCH signalling. Importantly, we find that pharmacological inhibition of γ-secretase promotes growth arrest in both Pten-null and Pten/Trp53-null prostate tumours by triggering cellular senescence. Altogether, our findings describe a novel pro-tumorigenic network that links PTEN loss to ADAM17 and NOTCH signalling, thus providing the rational for the use of γ-secretase inhibitors in advanced prostate cancer patients.

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Section: Discussionmentioning

confidence: 51%

Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

et al. 2016

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“…Hypoxia‐inducible factors (HIF‐1α and HIF‐2α) represent another low‐energy sensor that may play a role in both autophagy and the pathogenesis of diabetic nephropathy. Diabetes leads to upregulation of HIF‐1α, possibly because both hyperglycaemia and advanced glycation end products stimulate its transcription . However, it is unclear whether HIF‐1α upregulation represents an adaptive or deleterious response, as studies have reported conflicting results with respect to the role of hypoxia‐inducible factors in the genesis of diabetes‐related renal injury.…”

Section: Are Sglt2 Inhibitors Renoprotective Through An Action To Stimentioning

confidence: 99%

Interplay of adenosine monophosphate‐activated protein kinase/sirtuin‐1 activation and sodium influx inhibition mediates the renal benefits of sodium‐glucose co‐transporter‐2 inhibitors in type 2 diabetes: A novel conceptual framework

Packer

2020

Diabetes Obesity Metabolism

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Long-term treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors slows the deterioration of renal function in patients with diabetes. This benefit cannot be ascribed to an action on blood glucose, ketone utilization, uric acid or systolic blood pressure. SGLT2 inhibitors produce a striking amelioration of glomerular hyperfiltration. Although initially ascribed to an action of these drugs to inhibit proximal tubular glucose reabsorption, SGLT2 inhibitors exert renoprotective effects, even in patients with meaningfully impaired levels of glomerular function that are sufficient to abolish their glycosuric actions. Instead, the reduction in intraglomerular pressures may be related to an action of SGLT2 inhibitors to interfere with the activity of sodium-hydrogen exchanger isoform 3, thereby inhibiting proximal tubular sodium reabsorption and promoting tubuloglomerular feedback. Yet, experimentally, such an effect may not be sufficient to prevent renal injury. It is therefore noteworthy that the diabetic kidney exhibits an important defect in adenosine monophosphateactivated protein kinase (AMPK) and sirtuin-1 (SIRT1) signalling, which may contribute to the development of nephropathy. These transcription factors exert direct effects to mute oxidative stress and inflammation, and they also stimulate autophagy, a lysosomally mediated degradative pathway that maintains cellular homeostasis in the kidney. SGLT2 inhibitors induce both AMPK and SIRT1, and they have been shown to stimulate autophagy, thereby ameliorating cellular stress and glomerular and tubular injury. Enhanced AMPK/SIRT1 signalling may also contribute to the action of SGLT2 inhibitors to interfere with sodium transport mechanisms.The dual effects of SGLT2 inhibitors on AMPK/SIRT1 activation and renal tubular sodium transport may explain the protective effects of these drugs on the kidney in type 2 diabetes. K E Y W O R D Sautophagy, diabetic nephropathy, sirtuin-1, sodium-glucose co-transporter-2 inhibitor

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“…Furthermore, when the expression of Caspr1 was knocked down by siRNA, the luciferase activity of the critical fragment (−859 bp to −571 bp) of ADAM9 promoter was significantly reduced compared to the nonsilencing siRNA control, which is comparable to the effect observed with the whole −2,078 bp ADAM9 promoter ( Figure 3B). Several transcription factors, including p65, Sp1, Snail, and HIF1α, have been reported to be associated with the transcription of ADAM9 (Szalad et al, 2009;Li et al, 2015;Chang et al, 2017;Liu et al, 2017). Then, we analyzed whether the protein levels of these transcription factors were altered in Caspr1 knockout HBMECs.…”

Section: Adam9 Is Transcriptionally Downregulated By Caspr1 Depletionmentioning

confidence: 99%

Caspr1 Facilitates sAPPα Production by Regulating α-Secretase ADAM9 in Brain Endothelial Cells

Tang

Liu

et al. 2020

Front. Mol. Neurosci.

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High Glucose Up-regulates ADAM17 through HIF-1α in Mesangial Cells

Cited by 63 publications

References 53 publications

Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

Interplay of adenosine monophosphate‐activated protein kinase/sirtuin‐1 activation and sodium influx inhibition mediates the renal benefits of sodium‐glucose co‐transporter‐2 inhibitors in type 2 diabetes: A novel conceptual framework

Caspr1 Facilitates sAPPα Production by Regulating α-Secretase ADAM9 in Brain Endothelial Cells

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