Increased Soluble Flt-1 Correlates With Delayed Graft Function and Early Loss of Peritubular Capillaries in the Kidney Graft

Chapal, Marion; Néel, Mélanie; Borgne, Françoise Le; Meffray, Emanuelle; Carceles, Odette; Hourmant, Maryvonne; Giral, M.; Foucher, Yohann; Moreau, Anne; Fakhouri, Fádi

doi:10.1097/tp.0b013e31829f4772

Cited by 16 publications

(21 citation statements)

References 31 publications

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“…As the kidney functions worsen in the advanced stage of DN, the capillary endothelial cells give rise to capillary loss, tissue hypoxia, and oxidative stress. These would cause the reduction in the local nutrient supply and aggravate renal fibrosis ( Cao et al, 2012 ; Chapal et al, 2013 ). In addition, previous study showed that hyperactivated endothelial cells and high vascular permeability may also contribute to myofibroblasts ( Yamaguchi et al, 2012 ).…”

Section: The Role Of Lrg1 In Abnormal Angiogenesis Of Dnmentioning

confidence: 99%

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

et al. 2020

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Diabetic nephropathy (DN) is an important public health concern of increasing proportions and the leading cause of end-stage renal disease (ESRD) in diabetic patients. It is one of the most common long-term microvascular complications of diabetes mellitus that is characterized by proteinuria and glomerular structural changes. Angiogenesis has long been considered to contribute to the pathogenesis of DN, whereas the molecular mechanisms of which are barely known. Angiogenic factors associated with angiogenesis are the major candidates to explain the microvascular and pathologic finds of DN. Vascular endothelial growth factor A (VEGF-A), leucine-rich α-2-glycoprotein 1, angiopoietins and vasohibin family signal between the podocytes, endothelium, and mesangium have important roles in the maintenance of renal functions. An appropriate amount of VEGF-A is beneficial to maintaining glomerular structure, while excessive VEGF-A can lead to abnormal angiogenesis. LRG1 is a novel pro-angiogenic factors involved in the abnormal angiogenesis and renal fibrosis in DN. The imbalance of Ang1/Ang2 ratio has a role in leading to glomerular disease. Vasohibin-2 is recently shown to be in diabetes-induced glomerular alterations. This review will focus on current understanding of these angiogenic factors in angiogenesis and pathogenesis associated with the development of DN, with the aim of evaluating the potential of anti-angiogenesis therapy in patients with DN.

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Section: The Role Of Lrg1 In Abnormal Angiogenesis Of Dnmentioning

confidence: 99%

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

et al. 2020

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“…Ischemia reperfusion injury (IRI) causes acute kidney injury (AKI) with tubular and endothelial damage and leads to an early loss of peritubular capillaries (PTC) [ 1 ], decreased renal perfusion, and inflammation and fibrosis of the kidney [ 2 ]. In cadaveric kidney transplantation, ischemic allograft damage is correlated with impaired microcirculation in the peritubular capillaries [ 3 ] resulting in delayed graft function (DGF) [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice

et al. 2015

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Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20–50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

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“…In renal fibrosis, the significant changes in the structure and function of peritubular capillaries and the apoptosis of peritubular capillary endothelial cells give rise to capillary loss, tissue hypoxia and oxidative stress. At the same time, the loss of capillaries causes hypoxia or a reduction in the local nutrient supply, aggravating the renal fibrosis and resulting in kidney damage (Cao et al, 2012 ; Chapal et al, 2013 ). Moreover, changes in the renal tubular capillary structure and function lead to renal interstitial inflammation and a decrease or loss of renal tubular capillaries, eventually leading to further renal fibrosis.…”

Section: Klf4 and Renal Fibrosismentioning

confidence: 99%

The Role of Krüppel-like Factor 4 in Renal Fibrosis

Zhang

et al. 2015

Front. Physiol.

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Chronic kidney disease (CKD) caused by renal fibrosis is an important public health concern. It is therefore necessary to understand the molecular pathogenesis of renal fibrosis in order to develop novel therapeutic strategies. KLF4 is the most extensively studied factor among the various members of the Krüppel-like factor (KLF) family of zinc finger-containing transcription factors. Many studies have demonstrated that KLF4 inhibits the activation of myofibroblasts and exerts an inhibitory effect on fibrosis. However, other studies have indicated that KLF4 may promote renal fibrosis. These controversial results suggest that KLF4 may be crucially involved in the development of renal fibrosis, although the underlying mechanism(s) remain unclear. Here, we summarize the recent progress made in understanding the role of KLF4 in renal fibrosis. Together, these findings suggest that KLF4 may participate in the development of renal fibrosis, but that its inhibition of fibrosis is greater than its promotion of the condition, which suggests that KLF4 may serve as a novel therapeutic target for renal fibrosis.

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Increased Soluble Flt-1 Correlates With Delayed Graft Function and Early Loss of Peritubular Capillaries in the Kidney Graft

Abstract: sFlt-1 is a new nonimmunologic independent risk factor for DGF and PTC loss. Its inhibition may help improve the outcome of RT.

Cited by 16 publications

References 31 publications

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice

The Role of Krüppel-like Factor 4 in Renal Fibrosis

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