Mouse Models of Acute Kidney Injury

Acute Kidney Injury (AKI) is a poor prognosis in hospitalized patients that is associated with high degree of mortality. AKI is also a major risk factor for development of chronic kidney disease. Despite these serious complications associated with AKI there has not been a great amount of progress made over the last half-century. Here we have outlined and provided details on variety of mouse models of AKI. Some of the mouse models of AKI are renal pedicle clamping (ischemia reperfusion injury), Cisplatin induced nephrotoxicity, sepsis (LPS, cecal slurry, and cecal ligation and puncture), folic acid, and rhabdomyolysis. In this chapter we describe in detail the protocols that are used in our laboratories

Targeting ETosis by miR-155 inhibition mitigates mixed granulocytic asthmatic lung inflammation

Asthma is phenotypically heterogeneous with several distinctive pathological mechanistic pathways. Previous studies indicate that neutrophilic asthma has a poor response to standard asthma treatments comprising inhaled corticosteroids. Therefore, it is important to identify critical factors that contribute to increased numbers of neutrophils in asthma patients whose symptoms are poorly controlled by conventional therapy. Leukocytes release chromatin fibers, referred to as extracellular traps (ETs) consisting of double-stranded (ds) DNA, histones, and granule contents. Excessive components of ETs contribute to the pathophysiology of asthma; however, it is unclear how ETs drive asthma phenotypes and whether they could be a potential therapeutic target. We employed a mouse model of severe asthma that recapitulates the intricate immune responses of neutrophilic and eosinophilic airway inflammation identified in patients with severe asthma. We used both a pharmacologic approach using miR-155 inhibitor-laden exosomes and genetic approaches using miR-155 knockout mice. Our data show that ETs are present in the bronchoalveolar lavage fluid of patients with mild asthma subjected to experimental subsegmental bronchoprovocation to an allergen and a severe asthma mouse model, which resembles the complex immune responses identified in severe human asthma. Furthermore, we show that miR-155 contributes to the extracellular release of dsDNA, which exacerbates allergic lung inflammation, and the inhibition of miR-155 results in therapeutic benefit in severe asthma mice. Our findings show that targeting dsDNA release represents an attractive therapeutic target for mitigating neutrophilic asthma phenotype, which is clinically refractory to standard care