Stabilization of Hypoxia-Inducible Factor Ameliorates Glomerular Injury Sensitization after Tubulointerstitial Injury.

  title={Stabilization of Hypoxia-Inducible Factor Ameliorates Glomerular Injury Sensitization after Tubulointerstitial Injury.},
  author={Jun Zou and Jae Won Yang and Xiaoye Zhu and Jianyong Zhong and Ahmed Nahid Elshaer and Taiji Matsusaka and Ira Pastan and Volker H Haase and Hai-Chun Yang and Agnes B. Fogo},
  journal={Kidney international},
Previously, we found that mild tubulointerstitial injury sensitizes glomeruli to subsequent injury. Here, we evaluated whether stabilization of hypoxia-inducible factor-α (HIF-α), a key regulator of tissue response to hypoxia, ameliorates tubulointerstitial injury and impact on subsequent glomerular injury. Nep25 mice, which express the human CD25 receptor on podocytes under control of the nephrin promotor and develop glomerulosclerosis when a specific toxin is administered were used… 
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Pannexin 1 as a driver of inflammation and ischemia–reperfusion injury
This review describes how PanX1 functions in response to different pro-inflammatory stimuli, focusing mainly on signaling coordinated by the vasculature, and how Panx1 mediates ATP release by injured cells is discussed.
Glomerular subepithelial microparticles - a footprint for podocyte injury
  • Y. Kim, K. Huh, +10 authors Hyeon Joo Jeong
  • Medicine
    Ultrastructural pathology
  • 2021
ABSTRACT The aim of this study was to clarify the nature and clinical significance of glomerular subepithelial microparticles (SMPs), located between the basal surface of the podocytes and the
Disturbance of hypoxia response and its implications in kidney diseases.
  • Zuo-Lin Li, Bin Wang, Yi Wen, Qiu-Li Wu, L. Lv, Bi-Cheng Liu
  • Medicine
    Antioxidants & redox signaling
  • 2022
SIGNIFICANCE The disturbance of hypoxia response system is closely related to human diseases because it is essential for the maintenance of homeostasis. Given the significant role of the hypoxia


Tubulointerstitial fibrosis can sensitize the kidney to subsequent glomerular injury.
Increased atubular glomeruli and abnormal tubuloglomerular feedback significantly contribute to the crosstalk between the tubulointerstitium and glomersuli, supporting the concept that even mild preexisting tubulointerstitial injury sensitizesglomeruli to subsequent podocyte-specific injury.
Activation of hypoxia-inducible factor attenuates renal injury in rat remnant kidney.
  • Y. Song, Sun-Jin You, +6 authors K. Na
  • Medicine
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2010
Activation of HIF by DMOG halted the progression of proteinuria and attenuated structural damage by preventing podocyte injury in the remnant kidney model.
Chronic hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure.
  • M. Nangaku
  • Medicine
    Journal of the American Society of Nephrology : JASN
  • 2006
Therapeutic approaches that target the chronic hypoxia should prove effective against a broad range of renal diseases, and current modalities include the improvement of anemia with erythropoietin, the preservation of peritubular capillary blood flow by blockade of the renin-angiotensin system, and the use of antioxidants.
Tubular injury triggers podocyte dysfunction by β-catenin-driven release of MMP7.
It is demonstrated that beta-catenin-driven MMP-7 release from renal tubules promotes glomerular injury via direct degradation of the key slit diaphragm protein nephrin.
Peritubular capillary loss after mouse acute nephrotoxicity correlates with down-regulation of vascular endothelial growth factor-A and hypoxia-inducible factor-1 alpha.
It is speculated that that down-regulation of VEGF-A may be functionally-implicated in the progressive attrition of peritubular capillaries in areas of tubular atrophy and interstitial fibrosis; VEGf-A down- regulation correlates with a loss of HIF-1 alpha expression which itself occurs in the face of increased tissue hypoxia.
Hypoxia-Inducible Factor Activation Protects the Kidney from Gentamicin-Induced Acute Injury
In gentamicin-induced AKI, the activation of HIF by cobalt or DMOG attenuated renal dysfunction, proteinuria, and structural damage through a reduction of oxidative stress, inflammation, and apoptosis in renal tubular epithelial cells.
Preconditional activation of hypoxia-inducible factors ameliorates ischemic acute renal failure.
Evidence of principle is provided that preconditional activation of the HIF system protects against ischemic injury by inhibiting the activity of HIF hydroxylases.
Inhibition of hypoxia inducible factor hydroxylases protects against renal ischemia-reperfusion injury.
L-mimosine and dimethyloxalylglycine, two small molecules that activate HIF by inhibiting HIF hydroxylases, protected mouse kidneys from ischemia-reperfusion injury and may offer an effective strategy to protect the kidney from ischemic injury.
Chronic renal hypoxia after acute ischemic injury: effects of L-arginine on hypoxia and secondary damage.
It is suggested that a reduction in the peritubular capillary density after ARF results in a persistent reduction in renal Po(2) and that hypoxia may play an important role in progression of chronic renal disease after ARf.
Increased renal angiopoietin-1 expression in folic acid-induced nephrotoxicity in mice.
FA-induced nephropathy is associated with increased Ang-1 protein expression in renal epithelia and arteries and Tie-2-expressing capillaries near damaged cortical tubules undergo proliferation, and further experiments are required to establish whether these events are functionally related.