Mouse model of ischemic acute kidney injury: technical notes and tricks

Wei, Qingqing; Dong, Zheng

doi:10.1152/ajprenal.00352.2012

Cited by 244 publications

(224 citation statements)

References 78 publications

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“…It should be noted that the severity of ischemic AKI in murine models is influenced by several factors as recently reviewed. 45 In addition to the duration of ischemia, experimental conditions, including temperature control, animal strain, sex, and age, are important variables. In this study, surgery was performed by the same individual (D.Z.…”

Section: Mouse Ischemic Aki Modelsmentioning

confidence: 99%

“…45,46 This model avoids animal loss after severe AKI induced by bilateral IRI, because one kidney is intact at the time of injury. The UIRI model is well established and particularly suited to study AKI-CKD progression, because kidney function can be assessed after removing the intact kidney by nephrectomy.…”

Section: Manipulation Of Wnt/b-catenin Signaling In Vivomentioning

confidence: 99%

“…The UIRI model is well established and particularly suited to study AKI-CKD progression, because kidney function can be assessed after removing the intact kidney by nephrectomy. 45,46 The details of UIRI protocol are described in Figure 4A. Briefly, 10-week-old male C57BL/6 mice were subjected to UIRI by a similar protocol to bilateral IRI, except that only one renal pedicle was clipped for 30 minutes.…”

Section: Manipulation Of Wnt/b-catenin Signaling In Vivomentioning

confidence: 99%

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Sustained Activation of Wnt/β-Catenin Signaling Drives AKI to CKD Progression

Lin

Zhou²,

Tan

et al. 2015

JASN

202

214

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AKI is increasingly recognized as a major risk factor for progression to CKD. However, the factors governing AKI to CKD progression are poorly understood. In this study, we investigated this issue using moderate (20 minutes) and severe (30 minutes) ischemia/reperfusion injury (IRI) in mice. Moderate IRI led to acute kidney failure and transient Wnt/b-catenin activation, which was followed by the restoration of kidney morphology and function. However, severe IRI resulted in sustained and exaggerated Wnt/ b-catenin activation, which was accompanied by development of renal fibrotic lesions characterized by interstitial myofibroblast activation and excessive extracellular matrix deposition. To assess the role of sustained Wnt/b-catenin signaling in mediating AKI to CKD progression, we manipulated this signaling by overexpression of Wnt ligand or pharmacologic inhibition of b-catenin. In vivo, overexpression of Wnt1 at 5 days after IRI induced b-catenin activation and accelerated AKI to CKD progression. Conversely, blockade of Wnt/b-catenin by small molecule inhibitor ICG-001 at this point hindered AKI to CKD progression. In vitro, Wnt ligands induced renal interstitial fibroblast activation and promoted fibronectin expression. However, activated fibroblasts readily reverted to a quiescent phenotype after Wnt ligands were removed, suggesting that fibroblast activation requires persistent Wnt signaling. These results indicate that sustained, but not transient, activation of Wnt/b-catenin signaling has a decisive role in driving AKI to CKD progression. 27: 172727: -174027: , 201627: . doi: 10.1681 AKI is responsible for about 2 million deaths each year worldwide, and its incidence is rising. 1-3 AKI is increasingly common in critically ill patients, and those patients with severe AKI requiring dialysis have a mortality rate of .50%. In contrast to the traditional belief that survivors of AKI tend to fully recover renal function, there is growing evidence that patients who survive an episode of AKI will have a significant risk of developing progressive CKD and even ESRD. 1,2,4 Evidence is also mounting that the severity and frequency of AKI seem to be closely correlated with poor patient long-term outcome, 5,6 suggesting that AKI may be a predictive and causative factor for subsequent development of CKD. In this context, delineation of the underlying mechanisms governing the different courses of long-term outcome after AKI will not only shed new light on understanding the pathophysiology of AKI-CKD progression but also is instrumental in designing rational strategies for therapeutic intervention. J Am Soc NephrolWnt/b-catenin is a developmental signaling pathway that plays an essential role in regulating

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Section: Mouse Ischemic Aki Modelsmentioning

confidence: 99%

Section: Manipulation Of Wnt/b-catenin Signaling In Vivomentioning

confidence: 99%

Section: Manipulation Of Wnt/b-catenin Signaling In Vivomentioning

confidence: 99%

See 1 more Smart Citation

Sustained Activation of Wnt/β-Catenin Signaling Drives AKI to CKD Progression

Lin

Zhou²,

Tan

et al. 2015

JASN

202

214

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“…Significant reductions in creatinine levels in the IRCGA3 chlorogenic acid group were compared to the IR group (p <0.05) (Fig.1). Indicators of loss of renal function can be detected with elevated BUN and serum creatinine (Wei & Dong, 2012). Creatinine is a marker of filtration because it has the properties of the unbound protein, free filtered and not metabolized in the kidneys.…”

Section: Resultsmentioning

confidence: 99%

Chlorogenic Acid Attenuated Inflammatory Response in Kidney Disease with Ischemic Reperfusion Injury

Multazam¹,

Rini²

2017

Proceedings of the Health Science International Conference (HSIC 2017)

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Background: Ischemia reperfusion injury (I/R) at kidney has known as the primary cause of AKI and the most seeing through it. Chlorogenic acid (chlorogenic acid/CGA) is one of the most common polyphenols in the human diet. Chlorogenic acid has an antioxidant effect, antiapoptosis, antiinflammation, antifobrosis. Objective: To investigate the anti-inflammatory effect of chlorogenic acid on the kidneys with I/R injury. Method: Twenty male mice (3 months-old). The animals were divided into 4 groups, Ischemia reperfusion (IR, n = 5), I/R injury given CGA dose 3.5 mg/kg/BW (IRCGA1, n = 5), I/R injury given CGA dose of 7 mg/kg/BW (IRCGA2, n = 5), and I/R injury given

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“…Klinik olarak ARY gelişmesine neden olan iskemi, kalp debisinin azalması, renal vasküler oklüzyon ya da obstrüksiyon ile renal transplantasyon gibi durumlar sonucu ortaya çıkabilen bir durumdur. 106 İs-kemi ya da nefrotoksisite gibi durumlarda ARY düzleşmiş epitel ve tübüler genleşme sonucu ortaya çıkan "akut tübüler nekroz'' ile belirgindir. ARY, prerenal, renal (intrensek) ve postrenal yetmezlik olmak üzere üçe ayrılmaktadır.…”

Section: Renal İskemi̇/reperfüzyon Zedelenmesi̇unclassified

Myocardial and Renal Ischemia/Reperfusion Injury and Experimental Models: Review

Şenol¹,

Tunçtan²

2016

Turkiye Klinikleri J Pharm Sci

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Ö ÖZ ZE ET T Doku iskemisi, miyokard infarktüsü ve inme gibi klinik durumlarda ya da damar cerrahisi ve organ transplantasyonunda komplikasyon olarak ortaya çıkabilen bir durumdur. Reperfüzyon, iskemiye maruz kalan dokunun yeniden kanlanarak oksijenlenmesidir. İskemi/reperfüzyon (İ/R) zedelenmesi, kan akışının yeniden düzenlenmesiyle gelişen inflamatuar tepkilerin bir sonucudur. Erken evrede glikoliz yoluyla laktat üretimi sonucu hücre içi pH değeri düşer. Hücreleri nekroza karşı koruyan bu düşüş, reperfüzyon sıra-sında normal pH değerine yükseldiğinde iskemik hücrelerin ölümünü hızlandırır. Orta evre ise oksidatif stres ile belirgindir. Oksidatif stres belli bir eşiği aşarsa hücresel işlev bozukluğu, geri döndürülemez zedelenme ve hücre ölümü gerçekleşir. Geç evrede, inflamatuar hücreler ve adezyon molekülleri baskındır. Birçok inflamatuar molekül tarafından uyarılan nötrofil etkinliği İ/R süreci boyunca görülür. Miyokardiyal İ/R zedelenmesi miyokardiyal sersemleme (stunning), reperfüzyon aritmileri, miyositlerde nekroz ile koroner endotelyal ve mikrovasküler işlev bozukluğu gibi istenmeyen durumların ortaya çıkmasına yol açabilir. Deneysel olarak çalışılan konular miyokardiyal sersemleme, hibernasyon, reperfüzyon aritmileri ve ön koşul-lamadır. Akut renal yetmezlik (ARY) insanlarda yüksek mortalite ile ilişkili majör bir böbrek hastalığıdır. Kalp debisinin azalması, renal vasküler oklüzyon veya obstrüksiyon ile renal transplantasyon gibi durumların neden olduğu iskemi, ARY gelişmesine neden olabilir. Deneysel olarak çift taraflı (bilateral) ve tek taraflı (unilateral) renal İ/R zedelenmesi oluşturulabilmektedir. Çift taraflı iskemik ARY modeli insandaki patolojik duruma çok daha uygun olmasından dolayı yaygın olarak kullanılmaktadır. Bu çalışmada, ilaçla-rın miyokardiyal veya renal İ/R zedelenmesine bağlı olarak gelişen fizyopatolojik değişiklikler üzerindeki etkilerinin araştırılması amacıyla kullanılan deneysel modeller üzerinde durulmuştur.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : İskemi; reperfüzyon hasarı; oksidatif stres; inflamasyon; miyokardiyal reperfüzyon hasarı; akut böbrek hasarı A AB BS S T TR RA AC CT T Tissue ischemia is a condition that can occur with clinical conditions like myocardial infarction and stroke or as a complication of vascular surgery and organ transplantation. Reperfusion is reoxygenation of tissue exposed to ischemia by restoration of blood flow. Ischemia/reperfusion (I/R) injury is a consequence of inflammatory reaction induced by modulating blood flow. Intracellular pH falls as a result of lactate production through glycolysis at early stage. The decrease protecting cells against necrosis accelerates ischemic cell death at normal pH value during reperfusion. Intermediate phase is characterized by oxidative stress. If oxidative stress exceeds a certain threshold, cellular dysfunction, irreversible injury, and cell death occurs. At the late stage, inflammatory cells and adhesion molecules are dominant. Neutrophil activity stimulated by many inflammatory molecules ...

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Mouse model of ischemic acute kidney injury: technical notes and tricks

Cited by 244 publications

References 78 publications

Sustained Activation of Wnt/β-Catenin Signaling Drives AKI to CKD Progression

Sustained Activation of Wnt/β-Catenin Signaling Drives AKI to CKD Progression

Chlorogenic Acid Attenuated Inflammatory Response in Kidney Disease with Ischemic Reperfusion Injury

Myocardial and Renal Ischemia/Reperfusion Injury and Experimental Models: Review

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