Department of Urology, Zhongshan Hospital, Zhangjiang Technology Institute, Fudan University, Shanghai, China.
Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.
Adv Exp Med Biol. 2019;1165:101-116. doi: 10.1007/978-981-13-8871-2_6.
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.
肾移植是终末期肾病（ESRD）患者的一项改变生活的治疗措施。然而，移植肾不可避免地会经历初始急性肾损伤（AKI）和随后的慢性移植物功能障碍（CAD），逐渐发生纤维化并最终丧失功能。为了便于干预，揭示 AKI 和 CAD 的发病机制势在必行。我们研究了免疫、炎症和细胞凋亡在缺血再灌注损伤（IRI）和/或免疫抑制剂诱导的 AKI 模型中的作用及其与慢性损伤的关系。我们的研究主要集中在肾小管上皮细胞（TEC）上，TEC 既是损伤的被动受害者，也是主动参与者，并介导随后的修复或纤维化。针对不仅是成纤维细胞/肌成纤维细胞，还有 TEC 的靶点，可能是预防和治疗肾纤维化的根本策略。我们还评估了针对半胱天冬酶-3 的 siRNA 以及组织保护性促红细胞生成素衍生物 HBSP 和 CHBP 的潜在应用，旨在治疗 AKI 并预防 CAD 进展为 ESRD。已经取得了显著的进展，但 AKI 的及时诊断和精确治疗以及预防 CAD 进展为 ESRD 仍然极具挑战性。微阵列和测序分析等现代技术已被用于鉴定生物标志物，并可能有助于针对移植患者的单个细胞进行靶向治疗。
