Diabetic kidney disease induces transcriptome alterations associated with angiogenesis activity in human mesenchymal stromal cells.
Diabetic kidney disease induces transcriptome alterations associated with angiogenesis activity in human mesenchymal stromal cells.
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糖尿病肾脏疾病诱导与人间质基质细胞中血管生成活性相关的转录组改变。
DOI：
10.1186/s13287-023-03269-9
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发表时间：
2023-03-22
影响因子：
7.5
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中科院分区：
文献类型：
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优化血管生成活动的治疗干预可能会降低糖尿病肾病（DKD）患者的终末期肾病、严重肢体缺血和下肢截肢的发生率。自体间充质基质细胞（MSC）输注是一种很有前途的修复血管完整性的新疗法。然而，dkd相关因素，包括高血糖和尿毒症，可能在自体治疗方法中改变MSC血管生成修复能力。为了探索骨髓间充质干细胞在DKD中的血管生成活性，将从DKD受试者获得的脂肪组织来源的骨髓间充质干细胞的转录组与没有糖尿病或肾脏损害的年龄匹配的对照组进行比较。对MSC （DKD n = 29；对照n = 9）进行下一代RNA测序（RNA-seq），鉴定参与血管生成的差异表达（DE; adjusted p < 0.05, |log2fold change| |）信使RNA （mRNA）和microRNA (miRNA) （GeneCards）。利用人脐静脉内皮细胞在高糖和硫酸吲哚酚中培养高血糖尿毒症状态，体外评估了旁分泌介导的间充质干细胞条件培养基（MSCcm）的血管生成修复能力。RNA-seq分析显示，与Control-MSC相比，DKD-MSC中有133个DE mirna（77个上调，56个下调）和208个DE mirna（119个上调，89个下调）。有趣的是，调节血管生成并参与DKD发病机制的miRNA let-7a-5p与5种血管生成相关mrna （transgelin/TAGLN, thrombospondin 1/THBS1， lysyl氧化酶样4/LOXL4，胶原蛋白4A1/COL4A1和胶原蛋白8A1/COL8A1）相互作用。损伤内皮细胞与DKD-MSCcm孵育后，内皮细胞成管能力增强，迁移能力增强，粘附分子e -选择素、血管细胞粘附分子1和细胞间粘附分子1 mRNA表达降低。此外，血管生成修复效果在治疗组之间没有差异（DKD-MSCcm与Control-MSCcm）。与年龄匹配的对照组相比，来自DKD个体的MSC显示血管生成转录组改变。然而，血管生成修复的潜力可能被保留，支持自体间充质干细胞干预治疗需要增强血管生成活动的疾病，如DKD、糖尿病足溃疡和严重肢体缺血。在线版本包含补充材料，可在10.1186/s13287-023-03269-9获得。
Therapeutic interventions that optimize angiogenic activities may reduce rates of end-stage kidney disease, critical limb ischemia, and lower extremity amputations in individuals with diabetic kidney disease (DKD). Infusion of autologous mesenchymal stromal cells (MSC) is a promising novel therapy to rejuvenate vascular integrity. However, DKD-related factors, including hyperglycemia and uremia, might alter MSC angiogenic repair capacity in an autologous treatment approach. To explore the angiogenic activity of MSC in DKD, the transcriptome of adipose tissue-derived MSC obtained from DKD subjects was compared to age-matched controls without diabetes or kidney impairment. Next-generation RNA sequencing (RNA-seq) was performed on MSC (DKD n = 29; Controls n = 9) to identify differentially expressed (DE; adjusted p < 0.05, |log2fold change|> 1) messenger RNA (mRNA) and microRNA (miRNA) involved in angiogenesis (GeneCards). Paracrine-mediated angiogenic repair capacity of MSC conditioned medium (MSCcm) was assessed in vitro using human umbilical vein endothelial cells incubated in high glucose and indoxyl sulfate for a hyperglycemic, uremic state. RNA-seq analyses revealed 133 DE mRNAs (77 upregulated and 56 down-regulated) and 208 DE miRNAs (119 up- and 89 down-regulated) in DKD-MSC versus Control-MSC. Interestingly, miRNA let-7a-5p, which regulates angiogenesis and participates in DKD pathogenesis, interacted with 5 angiogenesis-associated mRNAs (transgelin/TAGLN, thrombospondin 1/THBS1, lysyl oxidase-like 4/LOXL4, collagen 4A1/COL4A1 and collagen 8A1/COL8A1). DKD-MSCcm incubation with injured endothelial cells improved tube formation capacity, enhanced migration, reduced adhesion molecules E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 mRNA expression in endothelial cells. Moreover, angiogenic repair effects did not differ between treatment groups (DKD-MSCcm vs. Control-MSCcm). MSC from individuals with DKD show angiogenic transcriptome alterations compared to age-matched controls. However, angiogenic repair potential may be preserved, supporting autologous MSC interventions to treat conditions requiring enhanced angiogenic activities such as DKD, diabetic foot ulcers, and critical limb ischemia. The online version contains supplementary material available at 10.1186/s13287-023-03269-9.
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影响因子：
7.4
作者：
Dzhoyashvili NA;Efimenko AY;Kochegura TN;Kalinina NI;Koptelova NV;Sukhareva OY;Shestakova MV;Akchurin RS;Tkachuk VA;Parfyonova YV
通讯作者：
Parfyonova YV
影响因子：
11.1
作者：
Hickson, LaTonya J.;Prata, Larissa G. P. Langhi;Kirkland, James L.
通讯作者：
Kirkland, James L.
影响因子：
4.3
作者：
Hickson, LaTonya J.;Rule, Andrew D.;Habermann, Elizabeth B.
通讯作者：
Habermann, Elizabeth B.
影响因子：
5.2
作者：
Eirin, Alfonso;Zhu, Xiang-Yang;Krier, James D.;Tang, Hui;Jordan, Kyra L.;Grande, Joseph P.;Lerman, Amir;Textor, Stephen C.;Lerman, Lilach O.
通讯作者：
Lerman, Lilach O.
DOI：
10.1038/nrc2561
发表时间：
2009-03
期刊：
Nature reviews. Cancer
影响因子：
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作者：
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