新月体型肾小球肾炎中肝X受体α的表达及意义

汪建平 张连珊* 冯路路 张一鸣 史永红 名取泰博 段惠军

解剖学报 ›› 2013, Vol. 44 ›› Issue (5) : 689-693.

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解剖学报 ›› 2013, Vol. 44 ›› Issue (5) : 689-693. DOI: 10.3969/j.issn.0529-1356.2013.05.021
组织学胚胎学发育生物学

新月体型肾小球肾炎中肝X受体α的表达及意义

  • 汪建平1 张连珊2* 冯路路2 张一鸣2 史永红2 名取泰博3 段惠军2
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Increased expression of lxrα protein in renal tubular epithelial cells of crescentic glomerulonephritis

  • WANG Jian-ping1 ZHANG Lian-shan 2* FENG Lu-lu2 ZHANG Yi-ming2 SHI Yong-hong2 NATORI Yasuhiro3 DUAN Hui-jun2
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摘要

目的 探讨肝X受体α(LXRα)在大鼠新月体型肾小球肾炎(GN)的表达及意义。方法 7周龄Wistar Kyoto 雄性大鼠40只随机分为两组。其中20只静脉注射兔抗大鼠肾小球基底膜抗体构建新月体型肾小球肾炎模型,20只作为正常对照。于注射抗体后第3、7、14、28和49天分别测定24h尿蛋白;免疫组织化学法检测第3、14、28和49天肾炎组和对照组大鼠肾组织LXRα表达;Western blotting和实时定量 PCR检测第14天肾炎肾皮质LXRα蛋白和mRNA表达变化。结果 注射抗体后第14天尿蛋白达(167.03±42.50)mg/24h;新月体百分比达65%;肾炎大鼠肾小管上皮细胞核LXRα表达明显增加;肾炎组肾皮质LXRα蛋白表达明显高于同期对照组,但肾皮质 mRNA表达则未见上调。 结论 新月体型肾炎肾小管上皮细胞核LXRα蛋白表达增强,说明肾小管LXR通路参与此型肾炎的发病过程。

Abstract

Objective To observe the change of expression of liver X receptorα(LXRα) protein and mRNA in crescentic glomelonephritis(GN). Methods Fourty male Wistar Kyoto rats were randomly divided into control group and GN group. Crescentic GN was induced by once intravenous injecting of rabbit anti-rat glomerular basement membrane(GBM) antibody in 20 rats as GN group. Proteinuria/24 hours were measured on days 3,7, 14, 28 and 49. Expression of LXRα protein in the kidney on days 3, 14, 28 and 49 was detected by immunohistochemistry, and LXRα protein and mRNA in renal cortex on day 14 were analysed by Western blotting and reverse transcription real time polymerse chain reaction (Real time-PCR). Results On days 14 after injection of GBM, crescent formation arrived 65% , and GN rats showed massive proteinuria(167.03±42.50)mg/24hours and marked lipid accumulation in renal tubular epithelial cells. There was extensive expression of LXRα protein in renal tubular epithelial cells of GN rats on day 14. No positive expression of LXRα protein was observed in macrophages and glomerular cells including mesangial cells, podocytes and endothelial cells. The expression of LXRα protein was up-regulated in renal cortex of GN rats on day 14 than that of normal rats. There was no significant difference of the LXRα mRNA level between two groups. Conclusion We provided for the first time the evidence that expression of LXRα protein in renal tubular epithelial cells of crescentic GN was increased. This finding suggests that LXR signaling pathway may be involved in the pathophysiologic process of this GN.

关键词

肝X受体 / 新月体型肾小球肾炎 / 免疫组织化学 / 免疫印迹法 / 实时定量PCR / Wistar Kyoto大鼠

Key words

Liver X receptor α / Crescentic glomerulonephritis / Immunohistochemistry / Western blotting / Real time-PCR / Wistar Kyoto rats

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汪建平 张连珊* 冯路路 张一鸣 史永红 名取泰博 段惠军. 新月体型肾小球肾炎中肝X受体α的表达及意义[J]. 解剖学报. 2013, 44(5): 689-693 https://doi.org/10.3969/j.issn.0529-1356.2013.05.021
WANG Jian-ping ZHANG Lian-shan* FENG Lu-lu ZHANG Yi-ming SHI Yong-hong NATORI Yasuhiro DUAN Hui-jun. Increased expression of lxrα protein in renal tubular epithelial cells of crescentic glomerulonephritis[J]. Acta Anatomica Sinica. 2013, 44(5): 689-693 https://doi.org/10.3969/j.issn.0529-1356.2013.05.021

参考文献

[1]Willy PJ, Umesono K, Ong ES, et al. LXR, a nuclear receptor that defines a distinct retinoid response pathway[J]. Genes Dev, 1995, 9(9): 1033-1045.
[2]Auboeuf D, Rieusset J,  Fajas L, et al. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-α in humans: no alteration in adipose tissue of obese and NIDDM patients[J]. Diabetes, 1997, 46(8): 1319-1327.
[3]Chen M, Bradley MN, Beaven SW, et al. Phosphorylation of the liver X receptors[J]. FEBS Lett, 2006, 580(20): 4835-4841.
[4]Joseph SB, Castrillo A, Laffitte BA, et al.Reciprocal regulation of inflammation and lipid metabolism by liver X receptors[J]. Nat Med, 2003, 9(2):213-219.
[5]Calkin AC, Tontonoz P. LXR signaling pathology and atherosclerosis[J].Arterioscler Thromb Vasc Biol, 2010, 30(8):1513-1518.
[6]Bensinger SJ, Tontonoz P. Integration of metabolism and inflammation by lipid-activated nuclear receptors[J]. Nature,2008,454(7203):470-477.
[7]Oosterveer MH, Grefhorst A,Groen AK,et al. The liver χ receptor: control of cellular lipid homeostasis and beyond: implications for drug design[J]. Prog Lipid Res,2010,49(4):342-352. 
[8]Smoak K, Madenspacher J, Jeyaseelan S, et al. Effects of liverχreceptor agonist treatment on pulmonary inflammation and host defense[J]. J Immunol , 2008, 180(5):3305-3312.
[9]Annicotte JS, Schoonjans K, Auwerx J. Expression of the liver X receptor alpha and beta in embryonic and adult mice[J]. Anat Rec A Discov Mol Cell Evol Biol, 2004, 277(2):312-316.
[10]Watanabe Y, Jiang SY, Takabe W, et al. Expression of the LXRalpha protein in human atherosclerotic lesions[J].Arterioscler Thromb Vasc Biol, 2005, 25(3):622-627. 
[11]Liu QY, Quinet E, Nambi P. Adipocyte fatty acid-binding protein(aP2), a newly identified LXR target gene, is induced by LXR agonist in human THP-1 cells[J]. Mol Cell Biochem,2007, 302(1-2):203-213.
[12]Crisafulli C, Mazzon E, Paterniti I, et al. Effects of Liver X receptor agonist treatment on signal transduction pathways in acute lung inflammation[J]. Respir Res,2010, 11(1):19-24. 
[13]Suzuki J, Ogawa M, Muto S, et al. Novel IkB kinase inhibitors for treatment of nuclear factor- kB -related diseases[J]. Expert Opin Investig Drugs, 2011, 20(3):395-405. 
[14]Ghisletti S, Huang W, Jepsen K, et al. Cooperative NCoR/SMRT interaction establish a corepressor-based strategy for integration if inflammatory and anti-inflammatory signaling patnway[J]. Genes Dev, 2009,23(6):681-693. 
[15]Kiss E, Popovic Z, Bedke J, et al. Suppression of chronic damage in renal allografts by Liver X receptor (LXR) activation relevant contribution of macrophage LXRα[J]. Am J Pathol, 2011,179(1):92-103.
[16]Wang Y, Moser AH, Shigenaga JK, et al.  Downregulation of liver X receptor-alpha in mouse kidney and HK-2 proximal tubular cells by LPS and cytokines[J].  J Lip Res,2005, 46(11):2377-2387. 
 

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