A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis.
A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis.
复制标题
局灶节段性肾小球硬化黑人患者载脂蛋白L1的肾小球转录组学研究
DOI：
10.1016/j.kint.2021.10.041
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发表时间：
2022-07
影响因子：
19.6
通讯作者：
Sampson, Matthew G.
中科院分区：
文献类型：
--
作者：
McNulty, Michelle T.;Fermin, Damian;Eichinger, Felix;Jang, Dongkeun;Kretzler, Matthias;Burtt, Noel P.;Pollak, Martin R.;Flannick, Jason;Weins, Astrid;Friedman, David J.;Sampson, Matthew G.
关键词：
载脂蛋白L1（APOL 1）相关的局灶节段性肾小球硬化症（FSGS）是黑人FSGS的主要形式。对于这种情况没有靶向治疗，部分原因是APOL 1对FSGS致病作用的分子机制尚未完全了解。研究患者肾脏中APOL 1 FSGS的转录组学景观是发现与人类疾病独特或最相关的基因和分子行为的重要途径。假设由高风险APOL 1基因型驱动的病理学反映在肾小球转录组的基因表达改变中，我们比较了16名高风险FSGS黑人患者与14名低风险APOL 1基因型黑人患者的15，703个基因的表达和共表达谱。来自APOL 1诱导的HEK 293细胞和正常人肾小球的表达数据用于追踪这些研究中发现的基因和分子途径。我们发现在高危患者中APOL 1和其他9个显著差异表达基因的表达增加。这包括斯钙素，它在线粒体和钙相关过程中发挥作用，沿着高风险和低风险APOL 1和代谢途径基因之间的差异相关性。与细胞外基质和免疫相关基因的相关性相似，但在高危FSGS中线粒体基因的共表达显著缺失，NF-κ B下调基因NKIRAS 1是最重要的枢纽基因，与NDUF家族（线粒体呼吸基因）和免疫相关基因（JAK-STAT）有较强的差异相关性。因此，线粒体基因调控的差异似乎是高风险和低风险FSGS黑人患者之间观察到的许多差异的基础。
Apolipoprotein L1 (APOL1)-associated focal segmental glomerulosclerosis (FSGS) is the dominant form of FSGS in Black individuals. There are no targeted therapies for this condition, in part because the molecular mechanisms underlying APOL1’s pathogenic contribution to FSGS are incompletely understood. Studying the transcriptomic landscape of APOL1 FSGS in patient kidneys is an important way to discover genes and molecular behaviors that are unique or most relevant to the human disease. With the hypothesis that the pathology driven by the high-risk APOL1 genotype is reflected in alteration of gene expression across the glomerular transcriptome, we compared expression and co-expression profiles of 15,703 genes in 16 Black patients with FSGS at high-risk vs 14 Black patients with a low-risk APOL1 genotype. Expression data from APOL1-inducible HEK293 cells and normal human glomeruli were used to pursue genes and molecular pathways uncovered in these studies. We discovered increased expression of APOL1 and nine other significant differentially expressed genes in high-risk patients. This included stanniocalcin, which has a role in mitochondrial and calcium-related processes along with differential correlations between high- and low-risk APOL1 and metabolism pathway genes. There were similar correlations with extracellular matrix- and immune-related genes, but significant loss of co-expression of mitochondrial genes in high-risk FSGS, and an NF-κB-down regulating gene, NKIRAS1, as the most significant hub gene with strong differential correlations with NDUF family (mitochondrial respiratory genes) and immune-related (JAK-STAT) genes. Thus, differences in mitochondrial gene regulation appear to underlie many differences observed between high- and low-risk Black patients with FSGS.
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影响因子：
4.3
作者：
Hudson NJ;Reverter A;Dalrymple BP
通讯作者：
Dalrymple BP
DOI：
10.1126/science.1193032
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Genovese G;Friedman DJ;Ross MD;Lecordier L;Uzureau P;Freedman BI;Bowden DW;Langefeld CD;Oleksyk TK;Uscinski Knob AL;Bernhardy AJ;Hicks PJ;Nelson GW;Vanhollebeke B;Winkler CA;Kopp JB;Pays E;Pollak MR
通讯作者：
Pollak MR
影响因子：
13.6
作者：
Granado, Daniel;Mueller, Daria;Weide, Thomas
通讯作者：
Weide, Thomas
影响因子：
3.4
作者：
Rogers SK;Shapiro LA;Tobin RP;Tow B;Zuzek A;Mukherjee S;Newell-Rogers MK
通讯作者：
Newell-Rogers MK
影响因子：
13.6
作者：
Kopp, Jeffrey B.;Nelson, George W.;Winkler, Cheryl A.
通讯作者：
Winkler, Cheryl A.