Implication of Peritubular Capillary Loss and Altered Expression of Vascular Endothelial Growth Factor in IgA Nephropathy

Namikoshi, Tamehachi; Satoh, Minoru; Horike, Hideyuki; Fujimoto, Sohachi; Arakawa, Sayaka; Sasaki, Tatsuya; Kashihara, Naoki

doi:10.1159/000088405

Cited by 40 publications

(39 citation statements)

References 56 publications

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“…Peritubular capillaries (PTCs) were assessed by immunohistochemical analysis using antibodies against CD34, which is an intrinsic endothelial cell antigen (17). As shown in Fig.…”

Section: Peritubular Capillariesmentioning

confidence: 99%

Deterioration of Renal Function by Chronic Heart Failure is Associated with Congestion and Oxidative Stress in the Tubulointerstitium

et al. 2011

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Objective We examined the hypothesis that renal congestion is responsible for the decline in renal function in patients with heart failure (HF) via tubulointerstitial inflammation. Methods First, in a longitudinal study, we retrospectively examined the relationship between cardiac functions and the decline of renal function during a period of 6.4±3.2 years in 20 patients who had a left ventricular ejection fraction of <40% and an estimated glomerular filtration ratio (eGFR) of <60 mL/min/1.73 m 2 . Second, we compared the renal histology in autopsy cases of HF-induced renal dysfunction (HF-RD), cases of nephrosclerosis (NSC) and cases of neither RD nor HF (controls) in a cross-sectional study. Third, we retrospectively examined renal function in HF patients with predominantly right, but not left, ventricular dysfunction.Results eGFR decreased at 9.4±4.6%/year in the cohort of the longitudinal study. The rate of eGFR decline was correlated with blood pressure and with diameter of the inferior vena cava (IVCd) (r=0.5) measured at the initial work-up. Multivariate analysis indicated that the IVCd is an independent determinant of decline of eGFR in HF. In the cross-sectional study, fibrosis, Rac1 expression, protein nitrosylation, and number of CD68-positive cells were increased in the tubulointerstitium in both cases of HF-RD and NSC. Peritubular capillaries in HF-RD were dilated by 35% without any change in density compared with those in the controls. In right sided HF, the reduction of IVCd after treatment was associated with improvement of eGFR. Conclusion Venous congestion may contribute to HF-induced deterioration of renal function by augmenting oxidative stress-mediated inflammation in the tubulointerstitium.

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“…Peritubular capillaries (PTCs) were assessed by immunohistochemical analysis using antibodies against CD34, which is an intrinsic endothelial cell antigen (17). As shown in Fig.…”

Section: Peritubular Capillariesmentioning

confidence: 99%

Deterioration of Renal Function by Chronic Heart Failure is Associated with Congestion and Oxidative Stress in the Tubulointerstitium

et al. 2011

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“…Indeed, clinical biopsy studies have shown an association between loss of tubular structure and function on the one hand and capillary rarefaction on the other. 11,12 Because of their limited replicative capacity, renal ECs are thought to be insufficiently capable to completely repair the injured endothelium of the peritubular capillary plexus after IRI. 13,14 Therefore, current therapeutic strategies to prevent microvascular loss have focused on the prevention of pericyte perturbation to reduce capillary rarefaction.…”

mentioning

confidence: 99%

Hematopoietic MicroRNA-126 Protects against Renal Ischemia/Reperfusion Injury by Promoting Vascular Integrity

Bijkerk¹,

Solingen²,

Boer³

et al. 2014

Journal of the American Society of Nephrology

105

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Ischemia/reperfusion injury (IRI) is a central phenomenon in kidney transplantation and AKI. Integrity of the renal peritubular capillary network is an important limiting factor in the recovery from IRI. facilitates vascular regeneration by functioning as an angiomiR and by modulating mobilization of hematopoietic stem/progenitor cells. We hypothesized that overexpression of miR-126 in the hematopoietic compartment could protect the kidney against IRI via preservation of microvascular integrity. Here, we demonstrate that hematopoietic overexpression of miR-126 increases neovascularization of subcutaneously implanted Matrigel plugs in mice. After renal IRI, mice overexpressing miR-126 displayed a marked decrease in urea levels, weight loss, fibrotic markers, and injury markers (such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin). This protective effect was associated with a higher density of the peritubular capillary network in the corticomedullary junction and increased numbers of bone marrow-derived endothelial cells. Hematopoietic overexpression of miR-126 increased the number of circulating Lin 2 /Sca-1 + /cKit + hematopoietic stem and progenitor cells. Additionally, miR-126 overexpression attenuated expression of the chemokine receptor CXCR4 on Lin 2 /Sca-1 + /cKit + cells in the bone marrow and increased renal expression of its ligand stromal cell-derived factor 1, thus favoring mobilization of Lin 2 /Sca-1 + /cKit + cells toward the kidney. Taken together, these results suggest overexpression of miR-126 in the hematopoietic compartment is associated with stromal cell-derived factor 1/CXCR4-dependent vasculogenic progenitor cell mobilization and promotes vascular integrity and supports recovery of the kidney after IRI.

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“…15,16) In addition, in the disease control group of this study, PTC networks were decreased, which were also clinically recognized in relation to the histological findings of interstitial injury in IgA nephropathy as a marker of poor prognosis. 17) Furthermore, renal dysfunction and elevated blood pressure were observed in the vehicle group. In a previous report, SKT was administered at doses 1.0 to 2.0 g/kg/d to stroke-prone spontaneously hypertensive rats.…”

Section: Discussionmentioning

confidence: 97%

Protective Effects of Shichimotsu-koka-To on Irreversible Thy-1 Nephritis

Ono

Kamikado

Morimoto

2013

Biological & Pharmaceutical Bulletin

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Oxidative stress and peritubular capillary (PTC) injury are involved in the progression of chronic kidney disease (CKD). We investigated protective effects of Shichimotsu-koka-To (SKT), a Japanese traditional Kampo prescription, against nephrosclerosis and hypertension on a CKD model due to irreversible nephritis. Six-week-old male Wistar rats were subjected to uninephrectomy, and to injection of rabbit anti-thymocyte serum. SKT treatment was continued for 15 weeks, blood pressure was measured, and then renal specimens were collected. PTC networks were detected by immunostaining for CD-31. And superoxide dismutase (SOD)-like activity in the tissue was evaluated. Blood pressure in the SKT group, as well as sham group, was significantly lower than with the vehicle. SKT markedly ameliorated renal function, which was evaluated with urea nitrogen clearance. Compared with the vehicle, SKT treatment lowered both the glomerular enlargement and hyper-cellularity by 80%, and decreased the extracellular matrix area by 75%. SKT treatment also suppressed tubular injury, and maintained PTC networks. Furthermore, SKT recovered SOD-like activity to the basal levels. These results suggest that SKT may be useful for the treatment of CKD during the progression to nephrosclerosis, through the mechanisms of anti-oxidative activity and maintenance of PTC networks.Key words hypertension; glomerular hypertrophy; peritubular capillary; chronic kidney disease; oxidative stressThe number of patients with end-stage renal failure undergoing dialysis is increasing worldwide. Recently, it has been accepted that patients with chronic kidney disease (CKD) also develop cardiovascular diseases, with increased risks of death, cardiovascular events, and hospitalization. 1) Improvement of the clinical outcomes of CKD patients is therefore important. In Japan, chronic glomerulonephritis and nephrosclerosis are major causes of renal failure after diabetic nephropathy, which is the most common cause.2) Hypertension is an important symptom which influences the outcome of CKD, and angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are beneficial to protect against renal injury in CKD.3)The herbal formula Shichimotsu-koka-To (SKT; Table 1) has occasionally been prescribed to treat hypertensive patients. 4)SKT was used for non-obesity hypertensive patients, and those complaining of the sensation of a rush of blood to the head, shoulder stiffness, tinnitus, and dull headache; however, in the last two or three decades, abundant new strong antihypertensive drugs have become available, and SKT has been used less. Recently, reevaluation of SKT treatment in combination with ACE-Is/ARBs drugs in CKD has begun. 5) In basic studies, SKT had an anti-hypertensive effect in Dahl strain rats.6) Enhanced serum NO x levels, and anti-oxidant activity through increasing superoxide dismutase (SOD)-like activity in the kidney by SKT were reported. 7,8) Previously, in a rat model of hypertensive nephrosclerosis induced by 5/6 nephrec...

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Implication of Peritubular Capillary Loss and Altered Expression of Vascular Endothelial Growth Factor in IgA Nephropathy

Cited by 40 publications

References 56 publications

Deterioration of Renal Function by Chronic Heart Failure is Associated with Congestion and Oxidative Stress in the Tubulointerstitium

Deterioration of Renal Function by Chronic Heart Failure is Associated with Congestion and Oxidative Stress in the Tubulointerstitium

Hematopoietic MicroRNA-126 Protects against Renal Ischemia/Reperfusion Injury by Promoting Vascular Integrity

Protective Effects of Shichimotsu-koka-To on Irreversible Thy-1 Nephritis

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