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尿液外泌体来源的 circRNAs 作为慢性肾纤维化的生物标志物。

Urinary exosomes derived circRNAs as biomarkers for chronic renal fibrosis.

机构信息

Department of Nephrology, Yi Ji Shan hospital affiliated to Wan Nan Medical College, Wuhu, China.

Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wan Nan Medical College), Wuhu, China.

出版信息

Ann Med. 2022 Dec;54(1):1966-1976. doi: 10.1080/07853890.2022.2098374.

DOI:10.1080/07853890.2022.2098374
PMID:35819256
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9291679/
Abstract

BACKGROUND

Chronic renal disease (CKD) is a common and irreversible loss of renal function. Renal fibrosis reflected the degree of renal dysfunction. However, the current biomarkers only characterize the renal function instead of indicating the fibrosis degree. The potential diagnostic value of urinary exosomes derived circRNAs for renal fibrosis needs to be further studied.

METHODS

Urine exosomes from 3 chronic kidney disease (CKD) patients without renal fibrosis and 3 renal fibrotic patients were collected and human circRNAs microarray analysis were performed to detect the circRNAs expression profile. 110 biopsy-proven CKD patients and 54 healthy controls were enrolled and urine exosomes derived RNA was isolated. The expression of hsa_circ_0036649 was measured and the correlation with renal function parameter and pathological indicators was performed. The receiver operating characteristic (ROC) curve for the diagnosis of renal fibrosis was calculated.

RESULTS

Human circRNAs microarray showed 365 circRNAs up expressed and 195 circRNAs down expressed in renal fibrotic patients compared to none fibrosis CKD patients. The expression of hsa_circ_0036649 was decreased in renal fibrotic patients according to RT-PCR and correlated with serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate and cystatin c. Further, the expression of hsa_circ_0036649 was correlated with the score of tubulointerstitial fibrosis (TIF) and the score of glomerular sclerosis. The ROC curve showed that hsa_circ_0036649 may predict renal fibrosis at a cut-off value of 0.597 with a sensitivity of 45.5% and specificity of 87.9%.

CONCLUSION

Expression of urinary exosomes derived hsa_circ_0036649 associated with the degree of renal fibrosis. Its potential role as a biomarker in CKD remained to be supported by further follow-up studies.Key MessagescircRNAs profile in urine exosomes in renal fibrosis patients was revealed.The expression of urine exosomes derived hsa_circ_0036649 was correlated to renal function and fibrosis degree.circRNAs derived from urinary exosomes may become a new research direction for biomarkers of renal fibrosis.

摘要

背景

慢性肾脏病(CKD)是一种常见且不可逆转的肾功能丧失。肾纤维化反映了肾功能的程度。然而,目前的生物标志物仅能描述肾功能,而不能指示纤维化程度。尿外泌体来源的 circRNAs 对肾纤维化的潜在诊断价值需要进一步研究。

方法

收集 3 例无肾纤维化的慢性肾脏病(CKD)患者和 3 例肾纤维化患者的尿外泌体,并进行人 circRNAs 微阵列分析,以检测 circRNAs 的表达谱。纳入 110 例经活检证实的 CKD 患者和 54 例健康对照者,并分离尿外泌体衍生的 RNA。测量 hsa_circ_0036649 的表达,并与肾功能参数和病理指标进行相关性分析。计算诊断肾纤维化的受试者工作特征(ROC)曲线。

结果

人 circRNAs 微阵列显示,与无纤维化 CKD 患者相比,肾纤维化患者中 365 个 circRNAs 表达上调,195 个 circRNAs 表达下调。根据 RT-PCR,hsa_circ_0036649 在肾纤维化患者中的表达降低,与血清肌酐、血尿素氮(BUN)、估算肾小球滤过率和胱抑素 C 相关。此外,hsa_circ_0036649 的表达与肾小管间质纤维化(TIF)评分和肾小球硬化评分相关。ROC 曲线显示,hsa_circ_0036649 在截断值为 0.597 时可预测肾纤维化,其灵敏度为 45.5%,特异性为 87.9%。

结论

尿外泌体来源的 hsa_circ_0036649 的表达与肾纤维化程度相关。其作为 CKD 生物标志物的潜在作用有待进一步的随访研究支持。

关键信息

揭示了肾纤维化患者尿外泌体中的 circRNAs 谱。尿外泌体来源的 hsa_circ_0036649 的表达与肾功能和纤维化程度相关。尿外泌体来源的 circRNAs 可能成为肾纤维化生物标志物的新研究方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/6b22894fa81e/IANN_A_2098374_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/e1e4ab3d454e/IANN_A_2098374_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/12bda149b743/IANN_A_2098374_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/16ab4bf7397d/IANN_A_2098374_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/b578bf9e0d7a/IANN_A_2098374_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/6fdaed87fd26/IANN_A_2098374_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/6b22894fa81e/IANN_A_2098374_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/e1e4ab3d454e/IANN_A_2098374_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/12bda149b743/IANN_A_2098374_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/16ab4bf7397d/IANN_A_2098374_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/b578bf9e0d7a/IANN_A_2098374_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/6fdaed87fd26/IANN_A_2098374_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a3/9291679/6b22894fa81e/IANN_A_2098374_F0006_C.jpg

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