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IgA 肾病患者肾内 microRNAs 的表达。

Intrarenal expression of microRNAs in patients with IgA nephropathy.

机构信息

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

Lab Invest. 2010 Jan;90(1):98-103. doi: 10.1038/labinvest.2009.118. Epub 2009 Nov 9.

Abstract

MicroRNAs (miRNAs) are noncoding, single-stranded RNA molecules that have important roles in a number of physiological and pathological processes. Previous studies have proved that miRNAs targeting ZEB1 and ZEB2 may repress epithelial-to-mesenchymal transition. In this work, we studied the intrarenal expression of miR-200 family, miR-205 and miR-192 in patients with immunoglobulin A (IgA) nephropathy. We studied 43 patients with biopsy-proven IgA nephropathy (IgA group). The intrarenal expression of miRNAs was quantified and compared with that of 15 patients with noninflammatory glomerulosclerosis (GS group) and 20 patients with nephrectomy for kidney cancer as controls (CTL group). The level of intrarenal miR-200c was downregulated, whereas the levels of intrarenal miR-141, miR-205 and miR-192 were upregulated in IgA but not GS group. Proteinuria significantly correlated with the intrarenal expression of miR-200c (r=-0.324, P=0.011) and glomerular filtration rate (GFR) significantly correlated with the intrarenal expression of miR-205 (r=-0.280, P=0.030). The degree of tubulointerstitial scarring correlated with miR-205 expression (r=0.389, P=0.021), whereas glomerulosclerosis correlated with miR-192 expression (r=-0.311, P=0.045). The rate of GFR decline significantly correlated with the intrarenal expression of miR-192 (r=0.373, P=0.015). The intrarenal expression of E-cadherin significantly correlated with the intrarenal expression of miR-200c (r=0.392, P=0.002). The results show that intrarenal expression of miR-200c, miR-141, miR-205 and miR-192 was diversely regulated and correlated with disease severity and progression in patients with IgA nephropathy. These miRNA species may be important in the pathogenesis and progression of IgA nephropathy.

摘要

微小 RNA(miRNAs)是一类非编码的单链 RNA 分子,在许多生理和病理过程中发挥着重要作用。先前的研究已经证明,靶向 ZEB1 和 ZEB2 的 miRNAs 可能会抑制上皮间质转化。在这项工作中,我们研究了 IgA 肾病患者肾组织中 miR-200 家族、miR-205 和 miR-192 的表达。我们研究了 43 例经活检证实的 IgA 肾病患者(IgA 组)。定量比较了 miRNA 在肾组织中的表达,并与 15 例非炎症性肾小球硬化症(GS 组)和 20 例因肾癌行肾切除术的患者(CTL 组)进行了比较。结果发现,IgA 组肾组织中 miR-200c 的水平下调,而 miR-141、miR-205 和 miR-192 的水平上调,但在 GS 组未发现这种变化。蛋白尿与肾组织中 miR-200c 的表达呈显著负相关(r=-0.324,P=0.011),肾小球滤过率(GFR)与肾组织中 miR-205 的表达呈显著负相关(r=-0.280,P=0.030)。肾小管间质瘢痕程度与 miR-205 的表达呈正相关(r=0.389,P=0.021),而肾小球硬化与 miR-192 的表达呈负相关(r=-0.311,P=0.045)。GFR 下降率与肾组织中 miR-192 的表达呈显著负相关(r=0.373,P=0.015)。E-钙黏蛋白的肾组织表达与 miR-200c 的表达呈显著正相关(r=0.392,P=0.002)。结果表明,miR-200c、miR-141、miR-205 和 miR-192 的肾组织表达受到不同程度的调节,并与 IgA 肾病患者的疾病严重程度和进展相关。这些 miRNA 可能在 IgA 肾病的发病机制和进展中发挥重要作用。

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