Pathogenesis of Chronic Allograft Dysfunction Progress to Renal Fibrosis
Kidney transplantation is a life-change measurement for the patients of end-stage renal disease (ESRD). However, the renal allograft cannot avoid initial acute kidney injury (AKI) and subsequent chronic allograft dysfunction (CAD), gradually develops fibrosis and eventually loses function. It is imperative to disclose the pathogenesis of AKI and CAD in order to facilitate interventions. We have studied the involvement of immunity, inflammation, and apoptosis in ischemia-reperfusion injury (IRI) and/or immunosuppressant induced AKI models, with associated chronic damage. Our research mainly focused on tubular epithelial cells (TECs) that are passive victims and also active participators in injury and mediate following repair or fibrosis. Targeting not only fibroblasts/myofibroblasts, but also TECs, might be a fundamental strategy to prevent and treat renal fibrosis. We have also evaluated the potential application of siRNA targeting caspase-3 and tissue protective erythropoietin derivatives, HBSP and CHBP, aiming to treat AKI and prevent CAD. Significant improvements have been obtained, but timely diagnosis and precise therapy of AKI and prevention of CAD progressing to ESRD are still very challenging. Modern technologies such as microarray and sequencing analysis have been used to identify biomarkers and potentially facilitate individual cell target treatment for transplant patients.
KeywordsFibrosis Tubular epithelia cell Kidney Inflammation
The studies cited in this chapter were supported by the Zhongshan Hospital of Fudan University; the Affiliated Hospital of Nantong University and the Medical School of Nantong University; and the University Hospitals of Leicester (UHL) and the University of Leicester. We also would like to acknowledge the support of various project grants such as the Kidney Care Appeal from UHL (to BY), the UK–China Fellowship for Excellence from the Department for Business Innovation and Skills (to BY), the National Natural Foundation of China (81400752 and 81770746 to CY and 81170689, 81570677 and 81873622 to BY), the National Key R&D Program of China (2018YFA0107502 to CY), the Medical and Health Talents Training Plan for the Excellent Youth of Shanghai Municipal (2018YQ50 to CY) and Shanghai Rising-Star Program (19QA1406300 to CY).
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