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独特的 III 型胶原重塑生物标志物反映了 IgA 肾病患者病理性肾脏组织改变的不同信息。

Unique Biomarkers of Collagen Type III Remodeling Reflect Different Information Regarding Pathological Kidney Tissue Alterations in Patients with IgA Nephropathy.

机构信息

Nordic Bioscience, 2730 Herlev, Denmark.

Department of Nephrology, First Faculty of Medicine and General University Hospital, Charles University in Prague, 128 08 Prague, Czech Republic.

出版信息

Biomolecules. 2023 Jul 8;13(7):1093. doi: 10.3390/biom13071093.

DOI:10.3390/biom13071093
PMID:37509129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10377132/
Abstract

Kidney fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix (ECM) remodeling. Collagen type III is one of the main ECM components of the interstitial matrix of the kidney. We hypothesized that measuring three biomarkers of collagen type III reflecting different aspects of this protein turnover (C3M, C3C, and PRO-C3) may provide different information about the fibrotic burden in patients with IgA nephropathy (IgAN). We examined a cohort of 134 patients with IgAN. The three collagen type III biomarkers were measured in serum (S) and in urine (U) samples taken on the same day before kidney biopsy was performed. Biopsies were evaluated for interstitial fibrosis and tubular atrophy, according to the Banff and MEST-C scores. S-PRO-C3 and S-C3C correlated with the degree of fibrosis in the biopsy, whereas U-C3M/Cr had an inverse correlation with fibrosis. U-C3M/Cr had the highest discrimination ability for advanced fibrosis, which was maintained after adjustment for the other collagen type III biomarkers, proteinuria, and serum creatinine. The data presented in this study indicate that measuring the different fragments of the same ECM protein and in different matrices provides a variety of information regarding pathological kidney tissue alterations in patients with IgAN.

摘要

肾脏纤维化是慢性肾脏病(CKD)的标志,其特征是细胞外基质(ECM)的失衡重塑。III 型胶原是肾脏间质基质中主要的 ECM 成分之一。我们假设,测量三种反映 III 型胶原不同方面的蛋白转化的 III 型胶原标志物(C3M、C3C 和 PRO-C3),可能会为 IgA 肾病(IgAN)患者的纤维化负担提供不同的信息。我们检查了 134 名 IgAN 患者的队列。在进行肾脏活检之前的同一天,从血清(S)和尿液(U)样本中测量了三种 III 型胶原生物标志物。根据 Banff 和 MEST-C 评分,对活检进行间质纤维化和肾小管萎缩评估。S-PRO-C3 和 S-C3C 与活检中的纤维化程度相关,而 U-C3M/Cr 与纤维化呈负相关。U-C3M/Cr 对晚期纤维化具有最高的鉴别能力,这种能力在调整了其他 III 型胶原生物标志物、蛋白尿和血清肌酐后仍然存在。本研究提供的数据表明,测量同一 ECM 蛋白的不同片段和不同基质,为 IgAN 患者的肾脏组织病理学改变提供了多种信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3392/10377132/575c2a6a894f/biomolecules-13-01093-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3392/10377132/374e4c6b5efa/biomolecules-13-01093-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3392/10377132/575c2a6a894f/biomolecules-13-01093-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3392/10377132/374e4c6b5efa/biomolecules-13-01093-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3392/10377132/575c2a6a894f/biomolecules-13-01093-g002.jpg

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2
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3
Considerations for understanding protein measurements: Identification of formation, degradation and more pathological relevant epitopes.
IgA血管炎肾病患儿尿外泌体miRNA-mRNA网络的构建及诊断效能评估
FASEB J. 2025 Apr 15;39(7):e70492. doi: 10.1096/fj.202403111R.
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Clin Kidney J. 2024 Dec 18;18(2):sfae413. doi: 10.1093/ckj/sfae413. eCollection 2025 Feb.
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