Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Expert Rev Proteomics. 2021 Jul;18(7):557-569. doi: 10.1080/14789450.2021.1962301. Epub 2021 Aug 6.
Main problems of kidney stone disease are its increasing prevalence and high recurrence rate after calculi removal in almost all areas around the globe. Despite enormous efforts in the past, its pathogenic mechanisms remain unclear and need further elucidations. Proteomics has thus become an essential tool to unravel such sophisticated disease mechanisms at cellular, subcellular, molecular, tissue, and whole organism levels.
This review provides abrief overview of kidney stone disease followed by updates on proteomics for investigating urinary stone modulators, matrix proteins, cellular responses to different types/doses of calcium oxalate (CaOx) crystals, sex hormones and other stimuli, crystal-cell interactions, crystal receptors, secretome, and extracellular vesicles (EVs), all of which lead to better understanding of the disease mechanisms. Finally, the future challenges and translation of these obtained data to the clinic are discussed.
Knowledge from urinary proteomics for exploring the important stone modulators (either inhibitors or promoters) will be helpful for early detection of asymptomatic cases for prompt prevention of symptoms, complications, and new stone formation. Moreover, these modulators may serve as the new therapeutic targets in the future for successful treatment and prevention of kidney stone disease by medications or other means of intervention.
肾结石疾病的主要问题是其在全球几乎所有地区的患病率不断增加，以及结石清除后复发率很高。尽管过去做出了巨大努力，但它的发病机制仍不清楚，需要进一步阐明。因此，蛋白质组学已成为揭示细胞、亚细胞、分子、组织和整个生物体水平等复杂疾病机制的重要工具。
本篇综述简要介绍了肾结石疾病，随后更新了蛋白质组学在研究尿结石调节剂、基质蛋白、细胞对不同类型/剂量草酸钙（CaOx）晶体、性激素和其他刺激物的反应、晶体-细胞相互作用、晶体受体、分泌组和细胞外囊泡（EVs）方面的应用，这些都有助于更好地了解疾病机制。最后，讨论了这些获得的数据在未来的挑战和向临床的转化。
从尿蛋白质组学中探索重要的结石调节剂（无论是抑制剂还是促进剂）的知识将有助于早期发现无症状病例，以便及时预防症状、并发症和新结石的形成。此外，这些调节剂将来可能成为新的治疗靶点，通过药物或其他干预手段成功治疗和预防肾结石疾病。
