1.Research update of Klotho in kidney injury and repair.
Acta Physiologica Sinica 2018;70(6):639-643
Klotho is highly expressed in the kidney, while soluble Klotho is detectable in the blood, urine, and cerebrospinal fluid, and has multiple hormone-like functions. The role of Klotho in kidney injury has attracted more and more attentions from researchers. Emerging evidence revealed that the transient deficiency of Klotho is an early event of acute kidney injury (AKI), whereas, in chronic kidney disease, this deficiency is sustained not only in the kidney, but also in other organ systems. Therefore, Klotho could be a potential biomarker for early diagnosis of AKI, as well as for its progression to chronic kidney disease. Moreover, Klotho might have therapeutic value to renal injury. Nevertheless, there are only few studies on the involvement of Klotho in post AKI repair. This review focused on the role of Klotho in not only kidney injury, but also its repair, in particular the relationship between Klotho and cell fate (autophagy/apoptosis/necrosis), repair/regeneration, Wnt/β-catenin and erythropoietin receptor, one of the Klotho effectors.
Acute Kidney Injury
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metabolism
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Biomarkers
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Disease Progression
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Glucuronidase
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physiology
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Humans
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Kidney
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metabolism
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pathology
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Signal Transduction
2.Progress of small ubiquitin-related modifiers in kidney diseases.
Ou LI ; Qian MA ; Fei LI ; Guang-Yan CAI ; Xiang-Mei CHEN ; Quan HONG
Chinese Medical Journal 2019;132(4):466-473
OBJECTIVE:
Small ubiquitin-related modifiers (SUMOs) are a group of post-translational modification proteins extensively expressed in eukaryotes. Abnormal SUMOylation can lead to the development of various diseases. This article summarizes the progress on research of the role of SUMOs in various types of kidney diseases to further increase the understanding of the regulatory functions of SUMOylation in the pathogenesis of kidney diseases.
DATA SOURCES:
This review was based on articles published in the PubMed databases up to January 2018, using the keywords including "SUMOs," "SUMOylation," and "kidney diseases."
STUDY SELECTION:
Original articles and critical reviews about SUMOs and kidney disease were selected for this review. A total of 50 studies were in English.
RESULTS:
SUMO participates in the activation of NF-κB inflammatory signaling pathway, playing a central regulatory role in the inflammation and progression of DN, and the secretion of various chemokines in AKI. SUMO involves in the regulation of TG2 and Nrf2 antioxidant stress, affecting renal tubular injury in AKI. SUMO affects the MAPK/ERK pathway, regulating intracellular signal transduction, modulating the transcription and expression of effector molecules in DN. SUMO contributes to the TGF-β/Smad pathway, leading to fibrosis of the kidney. The conjugate combination of SUMO and p53 regulates cell proliferation and apoptosis, and participates in the regulation of tumorigenesis. In addition, SUMOylation of MITF modulates renal tumors secondary to melanoma, Similarly, SUMOylation of tumor suppressor gene VHL regulates the occurrence of renal cell carcinoma in VHL syndrome.
CONCLUSIONS
Tissue injury, inflammatory responses, fibrosis, apoptosis, and tumor proliferation in kidney diseases all involve SUMOs. Further research of the substrate SUMOylation and regulatory mechanisms of SUMO in kidney diseases will improve and develop new treatment measures and strategies targeting kidney diseases.
Acute Kidney Injury
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etiology
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Carcinoma, Renal Cell
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etiology
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Diabetic Nephropathies
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etiology
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Fibrosis
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Humans
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Kidney
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pathology
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Kidney Diseases
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etiology
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metabolism
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Kidney Neoplasms
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etiology
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SUMO-1 Protein
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physiology
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Sumoylation
4.Heparin attenuated neutrophil infiltration but did not affect renal injury induced by ischemia reperfusion.
Cheung Soo SHIN ; Jeong Uk HAN ; Jung Lyul KIM ; Paul J SCHENARTS ; Lillian D TRABER ; Hal HAWKINS ; Daniel L TRABER
Yonsei Medical Journal 1997;38(3):133-141
Although heparin is better known as an anticoagulant, it also has several anti-inflammatory effects. Heparin is known to inhibit neutrophil adhesion, chemotaxis and oxygen free radical production. In addition, heparin is also known to act as an oxygen radical scavenger. Our hypothesis was that heparin would attenuate renal ischemia reperfusion injury. In this study, we investigated whether heparin had a protective effect on renal ischemia reperfusion injury. Sheep (n = 12) were prepared for the chronic study with venous, arterial and urinary catheters inserted. In addition, pneumatic occluders and ultrasonic flow probes were placed on renal arteries. After a 5-day recovery period, the sheep were randomized to either a heparin treatment group (400 IU/kg i.v. bolus 10 minutes before renal artery occlusion, followed by a continuous effusion 25,000 IU in 250 ml of 0.9% NaCl at 10 ml/hr, n = 6) or a control group (n = 6), which received an equivalent volume of 0.9% NaCl. All the sheep then underwent 90 minutes of bilateral renal ischemia followed by 24 hours of reperfusion. Blood urea nitrogen (BUN), serum creatinine (Scr), and creatinine clearance (CrCl) were determined at various intervals during both the ischemic and reperfusion periods. Kidney tissue samples were obtained at autopsy for histologic examination. As a result, there were significant differences in the degree of inflammation (1.50 +/- 1.24 Vs 0.50 +/- 0.79, P < 0.05) between the control and heparin treatment groups, but not in the degree of injury (2.83 +/- 0.44 Vs 2.33 +/- 0.28). In this study, heparin significantly attenuated polymorphonuclear leukocytes (PMNs) infiltration within the interstitium, but it did not affect the degree of renal damage as measured by urinary chemistries or renal tubular damage as assessed by histopathologic evaluation.
Animal
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Anticoagulants/pharmacology*
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Cell Movement/drug effects
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Female
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Heparin/pharmacology*
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Ischemia/pathology*
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Kidney/pathology
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Kidney/drug effects*
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Neutrophils/physiology
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Neutrophils/drug effects*
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Renal Circulation*
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Reperfusion Injury/pathology*
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Sheep
7.The significance of NO in renal cell apotosis following hind limbs ischemia/reperfusion in rats.
Guo-xian DUAN ; Lian-yuan ZHAG ; Li-jun ZHAO
Chinese Journal of Applied Physiology 2009;25(2):281-285
Animals
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Apoptosis
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Extremities
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blood supply
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Kidney
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pathology
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Male
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Nitric Oxide
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physiology
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Random Allocation
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Rats
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Rats, Wistar
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Reperfusion Injury
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pathology
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physiopathology
8.Clinical significance of TGF-β1 in children with primary IgA nephropathy.
Hong-Tao ZHU ; Liang RU ; Yan-Fang GUO
Chinese Journal of Contemporary Pediatrics 2014;16(7):749-753
OBJECTIVETo investigate the clinical significance of transforming growth factor-beta 1 (TGF-β1) in children with primary IgA nephropathy (IgAN).
METHODSThirty children who were diagnosed with primary IgAN by renal biopsy between May 2008 and October 2012 were included in the study. Thirty healthy children were used as the control group. Urinary and blood TGF-β1 levels were measured using enzyme-linked immunosorbent assay, and the protein expression of TGF-β1 in the renal tissue was measured by immunohistochemistry. The correlation between TGF-β1 levels in blood, urine, and renal tissue and their relationship with clinical indices were analyzed.
RESULTSChildren with primary IgAN had significantly higher urinary and blood TGF-β1 levels than the control group (P<0.01). Urinary TGF-β1 level was positively correlated with the pathological grade of renal tissue (r=0.557, P=0.001), and a significant positive correlation was also found between the TGF-β1 expression in the renal tissue and the pathological grade of renal tissue (r=0.682, P<0.01). There was no correlation between TGF-β1 levels in blood and renal tissue (r=0.038, P=0.844).
CONCLUSIONSUrinary TGF-β1 level is significantly positively correlated with the pathological severity of disease in children with primary IgAN. Clinical measurement of urinary TGF-β1 may be of great practical value in predicting the progression and prognosis of chronic nephropathy.
Adolescent ; Child ; Female ; Glomerulonephritis, IGA ; metabolism ; pathology ; Humans ; Kidney ; chemistry ; pathology ; Male ; Transforming Growth Factor beta1 ; analysis ; physiology ; urine
9.Effects of decline in renal function with age on the outcome of asymptomatic carotid plaque in healthy adults: a 5-year follow-up study.
Shi-Min JIANG ; Xue-Feng SUN ; Hong-Xia GU ; Yun-Shuang CHEN ; Chun-Sheng XI ; Xi QIAO ; Xiang-Mei CHEN
Chinese Medical Journal 2012;125(15):2649-2657
BACKGROUNDIt has been long suggested that abnormal clinical factors in the body, such as dyslipidemia and diabetes, can affect the presence of atherosclerosis. However, few studies on the effect of factors within the normal range, such as the loss of renal function with age, on the prevalence of atherosclerosis are few know in healthy individuals. The aim of this study was to investigate risk factors affecting the presence of asymptomatic carotid plaques in a middle-aged and elderly healthy population.
METHODSIn this regard, we prospectively evaluated 245 healthy individuals (98 males and 147 females) at baseline and after 5 years. Changes in the presence of carotid plaque between 2003 and 2008 were categorized into four groups, i.e. subjects without plaque at entry (n = 165): Group 1 (without plaque on two occasions, n = 129) and Group 2 (with nascent plaque at follow-up, n = 36); subjects with plaque at entry (n = 80); Group 3 (with plaque regression at follow-up, n = 29) and Group 4 (with plaque on two occasions, n = 51).
RESULTSUnivariate analysis showed that the positive rate of carotid plaques in males was higher than that in females at the baseline, and that a significantly inverse correlation existed between the prevalence rate of plaque and aging. Logistic regression analysis of cross-sectional research showed that independent risk factors for the prevalence of atherosclerosis were male gender, lower estimated glomerular filtration rate (eGFR) and higher low-density lipoprotein cholesterol (LDL-C) at the baseline, and older age and lower eGFR were involved in the presence of carotid plaques at follow-up point. However, logistic regression analysis of the longitudinal data showed that older age, decreased eGFR and increased systolic blood pressure (SBP) independently predicted the presence of carotid plaques after 5 years in subjects without plaque at entry. In addition, in subjects with plaque at entry, age, changes in eGFR and the baseline levels of serum albumin (ALB) and serum total bilirubin (BIL) dependently influenced the outcome of carotid plaque.
CONCLUSIONPhysiological decline of renal function, together with advancing age, was an independent risk factor which consistently affected the presence of carotid atherosclerosis in two categories of healthy individuals.
Adult ; Aged ; Aged, 80 and over ; Aging ; physiology ; Carotid Artery Diseases ; pathology ; physiopathology ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Kidney ; physiology ; physiopathology ; Male ; Middle Aged ; Prospective Studies ; Risk Factors
10.Interventions to improve chronic cyclosporine A nephrotoxicity through inhibiting renal cell apoptosis: a systematic review.
Zheng XIAO ; Cheng-wen LI ; Juan SHAN ; Lei LUO ; Li FENG ; Jun LU ; Sheng-fu LI ; Dan LONG ; You-ping LI
Chinese Medical Journal 2013;126(19):3767-3774
OBJECTIVETo reveal interventions for chronic cyclosporine A nephrotoxicity (CCN) and provide new targets for further studies, we analyzed all relevant studies about interventions in renal cell apoptosis.
DATA SOURCESWe collected all relevant studies about interventions for cyclosporine A (CsA)-induced renal cell apoptosis in Medline (1966 to July 2010), Embase (1980 to July 2010) and ISI (1986 to July 2010), evaluated their quality, extracted data following PICOS principles and synthesized the data.
STUDY SELECTIONWe included all relevant studies about interventions in CsA-induced renal cell apoptosis no limitation of research design and language) and excluded the duplicated articles, meeting abstracts and reviews without specific data.
RESULTSThere were three kinds of intervention, include anti-oxidant (sulfated polysaccharides, tea polyphenols, apigenin, curcumin, spirulina, etc), biologics (recombinant human erythropoietin (rhEPO), a murine pan-specific transforming growth factor (TGF)-beta-neutralizing monoclonal antibody1D11, cartilage oligomeric matrix protein (COMP)-angiopoietin-1 and hepatocyte growth factor (HGF) gene), and other drugs (spironolactone, rosiglitazone, pirfenidone and colchicine). These interventions significantly improved the CCN, renal cell apoptosis and renal dysfunction through intervening in four apoptotic pathways in animals or protected renal cells from apoptosis induced by CsA and increased cell survival through respectively four pathways in vitro.
CONCLUSIONSThere are three group interventions for CCN. Especially anti-oxidant drugs can significantly improve CCN, renal cell apoptosis and renal dysfunction. Many drugs can improve CCN through intervening in Fas/Fas ligand or mitochondrial pathway with sufficient evidences. Angiotensin II, nitric oxide (NO) and endoplasmic reticulum (ER) pathways will be new targets for CCN.
Animals ; Apoptosis ; drug effects ; Chronic Disease ; Cyclosporine ; adverse effects ; Humans ; Immunosuppressive Agents ; adverse effects ; Kidney ; drug effects ; pathology ; Mitochondria ; physiology ; Nitric Oxide ; physiology ; Signal Transduction ; fas Receptor ; physiology