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CD147在肾脏中的表达作为进行性IgA肾病的生物标志物。

CD147 renal expression as a biomarker for progressive IgAN.

作者信息

Sun Shiren, Zhao Ali, Li Rong, Du Rui, He Lijie, Sun Wenjuan, Wang Hanmin, Huang Chen

机构信息

Department of Nephrology, Xijing Hospital, Fourth Military Medical University, No. 169 Changle West Road, Xi'an, 710032, Shaanxi, China.

出版信息

J Nephrol. 2015 Jun;28(3):307-14. doi: 10.1007/s40620-014-0161-1. Epub 2014 Dec 16.

DOI:10.1007/s40620-014-0161-1
PMID:25510296
Abstract

BACKGROUND/AIMS: Recent studies have demonstrated that tubulointerstitial injury can predict renal outcomes better than the other histological parameters in patients with IgA nephropathy (IgAN). CD147 is a key regulator of renal tubulointerstitial fibrosis in cellular and animal models. However, it is not clear whether the expression of CD147 correlates with tubulointerstitial injury in IgAN patients.

METHODS

We analyzed the degree of CD147 expression and localization in renal biopsy tissues from IgAN patients and correlated their immunostaining scores with clinical and histological parameters.

RESULTS

Elevated CD147 expression was found in the basolateral membrane of renal tubules in IgAN patients; however, in normal kidney samples, positive staining for CD147 was not found in the tubular epithelial cells (P = 0.000). CD147 protein expression in the renal tubules showed a negative correlation with estimated glomerular filtration rate (eGFR; r = -0.600, P = 0.000) and a positive correlation with serum creatinine (Scr; r = 0.322, P = 0.002) and tubulointerstitial lesions (r = 0.525, P = 0.000). Moreover, a high level of CD147 correlated with the activation of Slug expression and E-cadherin repression in patients with IgAN. Kaplan-Meier survival curves showed that elevated CD147 expression was associated with decreased renal survival. Multivariate analyses further demonstrated that a high CD147 immunostaining score was an independent predictor of renal outcome in patients with IgAN (HR = 8.731, P = 0.041).

CONCLUSION

CD147 expression is associated with tubulointerstitial injury and predicts renal prognosis in IgA nephropathy. CD147 may be an early marker for tubulointerstitial injury IgA nephropathy.

摘要

背景/目的:近期研究表明,在IgA肾病(IgAN)患者中,肾小管间质损伤比其他组织学参数能更好地预测肾脏预后。在细胞和动物模型中,CD147是肾小管间质纤维化的关键调节因子。然而,尚不清楚CD147的表达与IgAN患者的肾小管间质损伤是否相关。

方法

我们分析了IgAN患者肾活检组织中CD147的表达程度和定位,并将其免疫染色评分与临床和组织学参数进行关联。

结果

在IgAN患者肾小管的基底外侧膜中发现CD147表达升高;然而,在正常肾脏样本中,未在肾小管上皮细胞中发现CD147阳性染色(P = 0.000)。肾小管中CD147蛋白表达与估计肾小球滤过率呈负相关(eGFR;r = -0.600,P = 0.000),与血清肌酐(Scr;r = 0.322,P = 0.002)和肾小管间质病变呈正相关(r = 0.525,P = 0.000)。此外,IgAN患者中高水平的CD147与Slug表达的激活和E-钙黏蛋白的抑制相关。Kaplan-Meier生存曲线显示,CD147表达升高与肾脏生存率降低相关。多因素分析进一步表明,高CD147免疫染色评分是IgAN患者肾脏预后的独立预测因子(HR = 8.731,P = 0.041)。

结论

CD147表达与肾小管间质损伤相关,并可预测IgA肾病的肾脏预后。CD147可能是IgA肾病肾小管间质损伤的早期标志物。

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本文引用的文献

1
CD147 induces angiogenesis through a vascular endothelial growth factor and hypoxia-inducible transcription factor 1α-mediated pathway in rheumatoid arthritis.CD147通过血管内皮生长因子和缺氧诱导转录因子1α介导的途径在类风湿性关节炎中诱导血管生成。
Arthritis Rheum. 2012 Jun;64(6):1818-27. doi: 10.1002/art.34341. Epub 2011 Dec 14.
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HAb18G/CD147 promotes epithelial-mesenchymal transition through TGF-β signaling and is transcriptionally regulated by Slug.HAb18G/CD147 通过 TGF-β 信号促进上皮-间充质转化,并通过 Slug 进行转录调控。
Oncogene. 2011 Oct 27;30(43):4410-27. doi: 10.1038/onc.2011.149. Epub 2011 May 2.
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跨膜信号分子在 IgA 肾病发病机制中发挥关键作用:一项加权基因共表达网络分析研究。
BMC Immunol. 2021 Dec 3;22(1):73. doi: 10.1186/s12865-021-00468-y.
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Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents.全面分析 IgA 肾病表达谱:鉴定潜在的生物标志物和治疗药物。
BMC Nephrol. 2021 Apr 19;22(1):137. doi: 10.1186/s12882-021-02356-4.
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Decreased Expression of Urinary Mammalian Target of Rapamycin mRNA Is Related to Chronic Renal Fibrosis in IgAN.尿哺乳动物雷帕霉素靶蛋白 mRNA 表达降低与 IgAN 慢性肾纤维化有关。
Dis Markers. 2019 Aug 14;2019:2424751. doi: 10.1155/2019/2424751. eCollection 2019.
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Circulating Tumor Cells for the Management of Renal Cell Carcinoma.循环肿瘤细胞在肾细胞癌治疗中的应用
Diagnostics (Basel). 2018 Sep 3;8(3):63. doi: 10.3390/diagnostics8030063.
Basigin/CD147 promotes renal fibrosis after unilateral ureteral obstruction.
Basigin/CD147 促进单侧输尿管梗阻后的肾纤维化。
Am J Pathol. 2011 Feb;178(2):572-9. doi: 10.1016/j.ajpath.2010.10.009.
4
Pathological predictors of prognosis in immunoglobulin A nephropathy: a review.免疫球蛋白A肾病预后的病理预测因素:综述
Curr Opin Nephrol Hypertens. 2009 May;18(3):212-9. doi: 10.1097/MNH.0b013e328329605c.
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Clin Exp Immunol. 2009 Apr;156(1):111-6. doi: 10.1111/j.1365-2249.2008.03868.x. Epub 2009 Jan 22.
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