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多囊肾病-1基因突变猫血清蛋白质组学分析

Analysis of serum proteomic in cats with polycystic kidney disease-1 gene mutation.

作者信息

Jiwaganont Palin, Jaturanratsamee Kotchapol, Thaisakun Siriwan, Roytrakul Sittiruk, Petchdee Soontaree

机构信息

Graduate School, Veterinary Clinical Studies Program, Faculty of Veterinary Medicine, Kasetsart University, Kamphaeng Saen, Nakorn Pathom, Thailand.

Graduate School, Bio-veterinary Science Program, Faculty of Veterinary Medicine, Kasetsart University, Thailand.

出版信息

Heliyon. 2024 Aug 2;10(15):e35577. doi: 10.1016/j.heliyon.2024.e35577. eCollection 2024 Aug 15.

Abstract

Feline autosomal dominant polycystic kidney disease (PKD) is common in Persian and Persian-cross cats. This study aims to investigate proteins that can be potential biomarkers for early disease diagnosis in cats with PKD1 heterozygous gene mutations and compare them with chronic kidney disease cats and normal wild-type cats. Thirty-three client-owned cats of variable breeds (ten PKD1 gene mutation cats, twelve wild-type cats with normal blood profiles, and eleven wild-type cats with chronic renal disease) were enrolled in this study. This study used serum-based proteomic profiling analysis in cats. Abdominal ultrasounds were examined in all cats. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). One hundred and fifty-nine proteins were significantly differentially expressed between each group. The proteins identified in this study are known to regulate the apoptosis pathway. The apoptosis regulator Bcl-2 (BCL2) was overexpressed in the chronic kidney disease (CKD) group, while apoptotic peptidase activating factor 1 (APAF1) and BCL2-associated X apoptosis regulator (BAX) were only expressed in the PKD group. Ingenuity pathway analysis revealed that proteins uniquely expressed in the PKD group were linked to the Wnt signaling pathway and MAPK pathway. Asparagine synthetase domain-containing and secreted frizzled-related proteins were interesting proteins that should be studied further for the possibility of a candidate protein for disease detection. The proteomic profiles identified in this study could be used as potential novel biomarkers for the early detection of PKD in cats.

摘要

猫常染色体显性多囊肾病(PKD)在波斯猫和波斯杂交猫中很常见。本研究旨在调查可作为PKD1杂合基因突变猫早期疾病诊断潜在生物标志物的蛋白质,并将它们与慢性肾病猫和正常野生型猫进行比较。本研究纳入了33只不同品种的客户拥有的猫(10只PKD1基因突变猫、12只血液指标正常的野生型猫和11只患有慢性肾病的野生型猫)。本研究对猫进行了基于血清的蛋白质组学分析。对所有猫进行了腹部超声检查。通过基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱和液相色谱-串联质谱(LC-MS/MS)进行蛋白质组学分析。每组之间有159种蛋白质存在显著差异表达。本研究中鉴定出的蛋白质已知可调节细胞凋亡途径。凋亡调节因子Bcl-2(BCL2)在慢性肾病(CKD)组中过表达,而凋亡肽酶激活因子1(APAF1)和BCL2相关X凋亡调节因子(BAX)仅在PKD组中表达。 Ingenuity通路分析显示,PKD组中独特表达的蛋白质与Wnt信号通路和MAPK通路有关。含天冬酰胺合成酶结构域和分泌型卷曲相关蛋白是有趣的蛋白质,应进一步研究其作为疾病检测候选蛋白的可能性。本研究中鉴定出的蛋白质组学图谱可作为猫PKD早期检测的潜在新型生物标志物。

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