Kota Satya K, Pernicone Elizabeth, Leaf David E, Stillman Isaac E, Waikar Sushrut S, Kota Savithri Balasubramanian
Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, Massachusetts.
Harvard Stem Cell Institute, Cambridge, Massachusetts.
J Am Soc Nephrol. 2017 Dec;28(12):3473-3478. doi: 10.1681/ASN.2016121265. Epub 2017 Aug 3.
AKI is a major cause of morbidity and mortality and an important contributor to the development and progression of CKD. Molecular biomarkers that improve the detection and prognostication of AKI are therefore required. We assessed the utility as such of BPI fold-containing family A member 2 (BPIFA2), also known as parotid secretory protein, which we identified a multiplex quantitative proteomics screen of acutely injured murine kidneys. In physiologic conditions, BPIFA2 is expressed specifically in the parotid glands and is abundant in salivary secretions. In our study, AKI induced expression in the kidneys of mice within 3 hours. Furthermore, we detected BPIFA2 protein in plasma and urine in these models as early as 6 hours after injury. However, renal injury did not induce the expression of in mice lacking , an immediate early gene expressed in the kidneys during AKI. Notably, patients with AKI had higher blood and urine levels of BPIFA2 than did healthy individuals. Together, our results reveal that BPIFA2 is a potential early biomarker of AKI.
急性肾损伤(AKI)是发病和死亡的主要原因,也是慢性肾脏病(CKD)发生和进展的重要因素。因此,需要能够改善AKI检测和预后评估的分子生物标志物。我们评估了含BPI折叠家族A成员2(BPIFA2,也称为腮腺分泌蛋白)在这方面的效用,该蛋白是我们在对急性损伤的小鼠肾脏进行多重定量蛋白质组学筛选时鉴定出来的。在生理条件下,BPIFA2特异性表达于腮腺,在唾液分泌中含量丰富。在我们的研究中,AKI在3小时内诱导小鼠肾脏中BPIFA2表达。此外,在这些模型中,我们早在损伤后6小时就在血浆和尿液中检测到了BPIFA2蛋白。然而,肾损伤并未在缺乏即刻早期基因Fos(AKI期间在肾脏中表达)的小鼠中诱导BPIFA2的表达。值得注意的是,AKI患者血液和尿液中的BPIFA2水平高于健康个体。我们的研究结果共同表明,BPIFA2是AKI的一种潜在早期生物标志物。