引用本文: |
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朱赛雅,牛阳阳,张晓琴,等.赖氨酰氧化酶样蛋白4在肾间质纤维化中的表达及意义[J].同济大学学报(医学版),2020,41(1):19-25. [点击复制]
- ZHU Sai-ya,NIU Yang-yang,ZHANG Xiao-qin,et al.Expression of LOXL4 and its roles in renal interstitial fibrosis[J].同济大学学报(医学版),2020,41(1):19-25. [点击复制]
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摘要: |
目的 赖氨酰氧化酶样蛋白4(lysyl oxidase-like protein 4, LOXL4)是赖氨酰氧化酶(lysyloxidase, LOX)家族的最新成员,本研究旨在观察LOXL4在肾脏纤维化形成中的表达及意义。方法 收集慢性肾脏病患者的肾活检标本,单侧输尿管结扎(unilateral ureteral ligation, UUO)大鼠;TGF-β1刺激大鼠肾成纤维细胞(NRK-49F)。通过q-PCR,Western印迹法和/或免疫组化等方法检测LOXL4的表达及作用。结果 患者肾脏纤维化组织中LOXL4沉积显著高于正常肾组织(P<0.01);与Sham组相比,UUO组大鼠肾脏LOXL4、Col1(collgen 1)表达水平明显升高(P<0.01);TGF-β1显著促进LOXL4、Col1的表达(P<0.01);转染LOXL4过表达质粒后,NRK-49F胶原表达水平明显增多(P<0.01);下调LOXL4后,胶原表达水平明显下降(P<0.01)。结论 在肾间质纤维化中LOXL4表达明显增加,其通过调控胶原纤维的表达而参与肾脏纤维化。 |
关键词: 赖氨酰氧化酶样蛋白4 转化生长因子β1 肾纤维化 细胞外基质 交联 |
DOI:10.16118/j.1008-0392.2020.01.004 |
投稿时间:2019-03-21 |
基金项目:国家自然科学基金(81873609、81600523、81700617) |
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Expression of LOXL4 and its roles in renal interstitial fibrosis |
ZHU Sai-ya,NIU Yang-yang,ZHANG Xiao-qin,YU Chen |
(Dept. of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China) |
Abstract: |
Objective To investigate the expression of lysyl oxidase-like protein 4(LOXL4) and its roles in renal fibrosis. Methods Renal biopsy specimens from patients with chronic kidney disease were collected. Sprague-Dawley rats were randomly divided into unilateral ureteral ligation(UUO) model group and sham operation(Sham) group;Rat kidney fibroblasts(NRK-49F) were stimulated with TGF-β1.The expression of LOXL4 mRNA and protein was detected by q-PCR, western blotting and/or immunohistochemistry, respectively. Results The expression of LOXL4 in fibrotic renal tissues of patients was significantly higher than that in normal renal tissues(P<0.01). Compared with Sham group, the expressions of LOXL4 and collgen1(Col1) in the kidney of UUO group of rats were significantly higher(P<0.01). TGF-β1 significantly promoted the expression of LOXL4 and Col1(P<0.01). After transfecting with LOXL4 expression plasmid, the expression of Col1 was increased significantly(P<0.01). There was significant reduction of Col1 expression in NRK-49F cells transfected with LOXL4 siRNA(P<0.01). Conclusion The expression of LOXL4 is up-regulated in renal interstitial fibrosis, which may be involved in renal fibrosis by regulating the expression of collagen fibers. |
Key words: lysyl oxidase-like protein 4 transforming growth factor β1 renal fibrosis extracellular matrix cross-linking |