Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Theranostics. 2022 May 13;12(9):4067-4080. doi: 10.7150/thno.72948. eCollection 2022.
Cyclophilin A (CyPA) or peptidylprolyl isomerase A (PPIA), an immunophilin with peptidyl-prolyl isomerase (PPIase) activity, is an abundant cellular protein widely expressed across various cell types and tissues, including the kidney. Expression of CyPA in the kidney is relatively higher in proximal tubular epithelial cells than others along the nephron. Alterations in expression and secretion of CyPA play important roles in physiological processes and pathophysiology of several diseases affecting the kidney. Herein, we provide a brief overview of CyPA structural biology and present the current update on its theranostic roles in various kidney diseases, including diabetic nephropathy, acute kidney injury, chronic kidney disease, renal fibrosis, and nephrotoxicity associated with organ transplantation. Notably, the diagnostic/prognostic role for urinary CyPA in several of these kidney diseases is promising. Finally, future perspectives on the CyPA research, especially targeting CyPA for therapeutics, are discussed. A comprehensive understanding of the theranostic roles of CyPA in kidney diseases is expected to provide novel insights into the design of new therapeutic interventions and prevention strategies.
亲环素 A(CyPA)或肽基脯氨酰顺反异构酶 A(PPIA),一种具有肽基脯氨酰顺反异构酶(PPIase)活性的免疫亲和素,是一种丰富的细胞蛋白,广泛表达于各种细胞类型和组织中,包括肾脏。在肾脏中,CyPA 的表达在近端肾小管上皮细胞中相对高于其他沿肾单位的细胞。CyPA 的表达和分泌的改变在影响肾脏的几种疾病的生理过程和病理生理学中起着重要作用。在此,我们简要概述了 CyPA 的结构生物学,并介绍了其在各种肾脏疾病中的治疗诊断作用的最新进展,包括糖尿病肾病、急性肾损伤、慢性肾脏病、肾纤维化和与器官移植相关的肾毒性。值得注意的是,尿 CyPA 在其中几种肾脏疾病中的诊断/预后作用很有前景。最后,讨论了 CyPA 研究的未来展望,特别是针对 CyPA 的治疗方法。全面了解 CyPA 在肾脏疾病中的治疗诊断作用有望为新的治疗干预和预防策略的设计提供新的见解。