Kidney Injury Molecule-1 Is Specifically Expressed in Cystically-Transformed Proximal Tubules of the PKD/Mhm (cy/+) Rat Model of Polycystic Kidney Disease

Gauer, Stefan; Urbschat, Anja; Gretz, Norbert; Hoffmann, Sigrid; Kränzlin, Bettina; Geiger, Helmut; Obermüller, Nicholas

doi:10.3390/ijms17060802

Cited by 18 publications

(13 citation statements)

References 31 publications

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“…Chronic kidney disease (CKD) is often caused by infections [1, 2], toxins [3, 4], and autoimmune diseases [5] and a major threat to public health [6]. CKD is involved with glomeruli [7, 8], tubules [9, 10], and interstitial tissue around the glomeruli and tubules [11]. CKD often results in glomerular injury because of the destruction of glomerular structure caused by high-level inflammatory cells [12, 13].…”

Section: Introductionmentioning

confidence: 99%

Cordyceps militarisImproves Chronic Kidney Disease by Affecting TLR4/NF-κB Redox Signaling Pathway

Sun

Dong

Jiang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Cordyceps militaris may show good promise in protecting against chronic kidney disease (CKD) but the molecular mechanism remains unclear. CKD risk is associated with the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. Cordycepin is the main component of Cordyceps militaris and may affect the TLR4/NF-κB pathway. Cordycepin was prepared by preparative HPLC. CKD patients were assigned into Cordyceps militaris (COG, 100 mg daily) and placebo (CG) groups. Cordycepin activity was measured using human embryo kidney cells (HEK293T). Biochemical indices, the levels of TLR4, NF-κB, cyclooxygenase-2 (COX2), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), were measured by real-time qRT-PCR, or ELISA kits and or Western blot. After 3-month treatment, cordycepin reduced the levels of urinal protein, blood urea nitrogen (BUN), and creatinine by 36.7%±8.6%, 12.5%±3.2%, and 18.3%±6.6%, respectively (P<0.05). Cordyceps militaris improved lipid profile and redox capacity of CKD patients by reducing the serum levels of TG, TC, and LDL-C by 12.8%±3.6%, 15.7%±4.1%, and 16.5%±4.4% and increasing the HDL-C level by 10.1%±1.4% in the COG group when compared with the CG group, respectively (P<0.05). The serum levels of cystatin-C (Cys-C), myeloperoxidase (MPO), and malondialdehyde (MDA) were reduced by 14.0%±3.8%, 26.9%±12.3%, and 19.7%±7.9% while nitric oxide (NO) and superoxide dismutase (SOD) were increased by 12.5%±2.9% and 25.3%±13.4% in the COG group when compared with the CG group, respectively (P<0.05). Cordycepin reduced the levels of TLR4, NF-κB, COX2, TNF-α, and IL-1β in HEK293T cells too (P<0.05). However, cordycepin could not affect the levels anymore if TLR4 was silenced. Cordyceps militaris protected against CKD progression by affecting the TLR4/NF-κB lipid and redox signaling pathway via cordycepin.

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Section: Introductionmentioning

confidence: 99%

Cordyceps militarisImproves Chronic Kidney Disease by Affecting TLR4/NF-κB Redox Signaling Pathway

Sun

Dong

Jiang

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…KIM-1 is a marker of acute or chronic tubulointerstitial damage [36]. In an animal study on the efficacy of KIM-1 as an early diagnostic biomarker for acute kidney injury, urinary KIM-1 levels have been shown to be five-fold higher without a significant decrease in creatinine levels or an increase in proteinuria [37].…”

Section: Discussionmentioning

confidence: 99%

The effects of Urtica dioica L. ethanolic extract against urinary calculi in rats

KELEŞ¹,

Şen²,

Ertaş³

et al. 2020

jrp

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Nephrolithiasis is common urological problem and stone formation has multiple underlying pathogenetic factors. We investigated the possible preventive and therapeutic effects of Urtica dioica ethanol extract (UD) on ethylene glycol-induced nephrolithiasis model in rats. Sprague-Dawley rats were divided into four groups (n = 10). The control group was given normal drinking water for 8 weeks and was administered vehicle by gastric gavage. Stone formation was induced by adding 0.75% ethylene glycol (EG) to their drinking water. UD (700 mg/kg) was given orally for 8 weeks to the preventive group and for last 4 weeks to the treatment group, respectively. At the end of the experiment, urine, blood samples and kidney tissues were obtained. In 24-hour urine samples, calcium and citrate levels were decreased and oxalate levels were increased in EG group whereas UD treatment groups reversed these parameters back to control levels. In addition, serum levels of creatinine and urea were increased in EG group, while UD significantly reduced these parameters. Malondialdehyde, 8-hydroxydeoxyguanosine and tumor necrosis alpha levels, and caspase-3 and N-acetyl-β-glucosaminidase activities were elevated in EG group and showed a decrease in UD treated groups. Glutathione level was decreased in EG group, whereas it was increased in UD preventive group. Histological examination showed an improvement in UD treated groups. Our results suggest that UD is effective both in prevention and treatment for kidney stones. The mechanism underlying this effect may be the antioxidant effect of UD and the effect on the concentration of stone-forming components in the urine.

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“…Kim-1 encodes a membrane protein, which is up-regulated in proliferating and dedifferentiated tubular cells after renal ischemia (25). Kim-1 is postulated to be a potential biomarker for ADPKD progression (15,39).…”

Section: Discussionmentioning

confidence: 99%

Polycystin-1 dysfunction impairs electrolyte and water handling in a renal precystic mouse model for ADPKD

Verschuren

Mohammed

Leonhard

et al. 2018

American Journal of Physiology-Renal Physiology

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The PKD1 gene encodes polycystin-1 (PC1), a mechanosensor triggering intracellular responses upon urinary flow sensing in kidney tubular cells. Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD). The involvement of PC1 in renal electrolyte handling remains unknown since renal electrolyte physiology in ADPKD patients has only been characterized in cystic ADPKD. We thus studied the renal electrolyte handling in inducible kidney-specific Pkd1 knockout (iKsp- Pkd1) mice manifesting a precystic phenotype. Serum and urinary electrolyte determinations indicated that iKsp- Pkd1 mice display reduced serum levels of magnesium (Mg), calcium (Ca), sodium (Na), and phosphate (P) compared with control ( Pkd1) mice and renal Mg, Ca, and P wasting. In agreement with these electrolyte disturbances, downregulation of key genes for electrolyte reabsorption in the thick ascending limb of Henle's loop (TA;, Cldn16, Kcnj1, and Slc12a1), distal convoluted tubule (DCT; Trpm6 and Slc12a3) and connecting tubule (CNT; Calb1, Slc8a1, and Atp2b4) was observed in kidneys of iKsp- Pkd1 mice compared with controls. Similarly, decreased renal gene expression of markers for TAL ( Umod) and DCT ( Pvalb) was observed in iKsp- Pkd1 mice. Conversely, mRNA expression levels in kidney of genes encoding solute and water transporters in the proximal tubule ( Abcg2 and Slc34a1) and collecting duct ( Aqp2, Scnn1a, and Scnn1b) remained comparable between control and iKsp- Pkd1 mice, although a water reabsorption defect was observed in iKsp- Pkd1 mice. In conclusion, our data indicate that PC1 is involved in renal Mg, Ca, and water handling and its dysfunction, resulting in a systemic electrolyte imbalance characterized by low serum electrolyte concentrations.

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Kidney Injury Molecule-1 Is Specifically Expressed in Cystically-Transformed Proximal Tubules of the PKD/Mhm (cy/+) Rat Model of Polycystic Kidney Disease

Cited by 18 publications

References 31 publications

Cordyceps militarisImproves Chronic Kidney Disease by Affecting TLR4/NF-κB Redox Signaling Pathway

Cordyceps militarisImproves Chronic Kidney Disease by Affecting TLR4/NF-κB Redox Signaling Pathway

The effects of Urtica dioica L. ethanolic extract against urinary calculi in rats

Polycystin-1 dysfunction impairs electrolyte and water handling in a renal precystic mouse model for ADPKD

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