Histologically resolved small RNA maps in primary focal segmental glomerulosclerosis indicate progressive changes within glomerular and tubulointerstitial regions.
Histologically resolved small RNA maps in primary focal segmental glomerulosclerosis indicate progressive changes within glomerular and tubulointerstitial regions.
复制标题
DOI：
10.1016/j.kint.2021.12.030
复制
发表时间：
2022-04
影响因子：
19.6
通讯作者：
Liang M
中科院分区：
文献类型：
--
作者：
Williams AM;Jensen DM;Pan X;Liu P;Liu J;Huls S;Regner KR;Iczkowski KA;Wang F;Li J;Gallan AJ;Wang T;Baker MA;Liu Y;Lalehzari N;Liang M
病理异质性在临床组织标本中很常见，并且使从标本获得的分子数据的解释复杂化。作为一个典型的例子，肾活检标本通常包含肾小球和肾小管间质区域，具有不同程度的组织学损伤，包括一些组织学正常的区域。我们推断，具有特定组织学损伤评分的肾组织区域的分子谱可以为肾损伤进展提供新的见解。因此，我们开发了一种策略，对福尔马林固定、石蜡包埋的肾穿刺活检中单独评分的肾小球和肾小管间质区域进行小RNA深度测序分析。这种方法被应用于研究局灶节段性肾小球硬化症（FSGS），成人肾病综合征的主要原因。大量的小RNA，包括microRNA、3' tRNA片段（tRF）、5'-tRF和线粒体tRF，在来自FSGS患者和匹配的健康对照的组织学上不可区分的组织区域之间差异表达。大多数tRF在FSGS中上调。在FSGS中，具有不同组织学评分的组织区域之间存在几种小RNA的差异表达。值得注意的是，随着组织学损伤水平的增加，分别在肾小球和肾小管间质区域中，miR-21- 5 p进行性上调，miR-192- 5 p进行性下调。这项研究标志着第一个在组织学特征的肾小球和肾小管间质区域进行的基因组规模的分子分析。因此，FSGS中组织学正常肾脏区域的实质性分子变化可能有助于启动组织损伤或代表代偿机制。此外，几种小RNA可能有助于随后的肾小球和肾小管间质损伤的进展，并且组织学定位小RNA谱可用于分析任何疾病中的组织标本。
Pathological heterogeneity is common in clinical tissue specimens and complicates the interpretation of molecular data obtained from the specimen. As a typical example, a kidney biopsy specimen often contains glomeruli and tubulointerstitial regions with different levels of histological injury, including some that are histologically normal. We reasoned that the molecular profiles of kidney tissue regions with specific histological injury scores could provide new insights into kidney injury progression. Therefore, we developed a strategy to perform small RNA deep sequencing analysis for individually scored glomerular and tubulointerstitial regions in formalin-fixed, paraffin-embedded kidney needle biopsies. This approach was applied to study focal segmental glomerulosclerosis (FSGS), the leading cause of nephrotic syndrome in adults. Large numbers of small RNAs, including microRNAs, 3’ tRNA fragments (tRFs), 5’-tRFs, and mitochondrial tRFs, were differentially expressed between histologically indistinguishable tissue regions from patients with FSGS and matched healthy controls. A majority of tRFs were upregulated in FSGS. Several small RNAs were differentially expressed between tissue regions with different histological scores in FSGS. Notably, with increasing levels of histological damage, miR-21–5p was upregulated progressively and miR-192–5p was downregulated progressively in glomerular and tubulointerstitial regions, respectively. This study marks the first genome scale molecular profiling conducted in histologically characterized glomerular and tubulointerstitial regions. Thus, substantial molecular changes in histologically normal kidney regions in FSGS might contribute to initiating tissue injury or represent compensatory mechanisms. In addition, several small RNAs might contribute to subsequent progression of glomerular and tubulointerstitial injury, and histologically mapping small RNA profiles may be applied to analyze tissue specimens in any disease.
登录
查看更多内容
影响因子：
13.6
作者：
Lai, Jennifer Y.;Luo, Jihghui;Bitzer, Markus
通讯作者：
Bitzer, Markus
影响因子：
13.6
作者：
Baker, Maria Angeles;Davis, Seth J.;Liang, Mingyu
通讯作者：
Liang, Mingyu
影响因子：
14.9
作者：
Mladinov D;Liu Y;Mattson DL;Liang M
通讯作者：
Liang M
DOI：
10.1073/pnas.1206761110
发表时间：
2013-01-22
影响因子：
11.1
作者：
Maute, Roy L.;Schneider, Christof;Dalla-Favera, Riccardo
通讯作者：
Dalla-Favera, Riccardo
DOI：
10.1001/jama.2015.18359
发表时间：
2016-01-26
期刊：
JAMA
影响因子：
--
作者：
Kotchen TA;Cowley AW Jr;Liang M
通讯作者：
Liang M