Diabetes-induced glucolipotoxicity impairs wound healing ability of adipose-derived stem cells-through the miR-1248/CITED2/HIF-1α pathway
Diabetes-induced glucolipotoxicity impairs wound healing ability of adipose-derived stem cells-through the miR-1248/CITED2/HIF-1α pathway
复制标题
糖尿病引起的糖脂毒性通过 miR-1248/CITED2/HIF-1α 途径损害脂肪干细胞的伤口愈合能力
DOI：
10.18632/aging.103053
复制
发表时间：
2020-04
期刊：
影响因子：
--
通讯作者：
Chengliang Deng
中科院分区：
文献类型：
--
作者：
Shune Xiao;Dan Zhang;Zhiyuan Liu;Wenhu Jin;Guangtao Huang;Zairong Wei;Dali Wang;Chengliang Deng
尽管是用于伤口愈合的间充质干细胞（MSC）移植疗法的有吸引力的细胞类型，但来自糖尿病（DM）患者的人脂肪源性干细胞（hADSC）由于糖尿病诱导的糖脂毒性而导致干细胞活性的显著保留。我们探讨了糖尿病和含有AGEs的培养基对hADSCs的细胞活性、表型、多能性、血管生成潜力和治疗效果的影响。然后，通过miRNA微阵列分析筛选出miRNA-1248，进一步研究调控hADSCs伤口愈合能力的核心分子通路。从DM患者分离的或在含有AGEs的培养基中体外培养的hADSC在干细胞治疗中表现出降低的有效性。miRNA-1248在糖尿病患者hADSC中的表达降低，因此不能正向调节干细胞活性、分化功能和促血管生成作用。这同时增加了CITED 2（HIF-1α抑制剂）的表达，从而影响促进血管生成、细胞增殖和伤口愈合的生长因子。总之，我们的数据表明，hADSC的葡萄糖脂毒性受损的伤口愈合能力可能通过miR-1248/CITED 2/HIF-1α途径发生。miRNA-1248有可能成为糖尿病患者伤口愈合或恢复糖尿病hADSC伤口愈合能力的新治疗靶点。
Despite being an attractive cell type for mesenchymal stem cell (MSC) transplantation therapy for wound healing, human adipose-derived stem cells (hADSCs) from diabetes mellitus (DM) patients result in remarkable retention of stem cell activity due to diabetes-induced glucolipotoxicity. We explored the effect of diabetes and medium containing AGEs on the cell activity, phenotype, multipotency, angiogenic potential, and the therapeutic effect of hADSCs. Then, miRNA-1248 was selected by miRNA microarray analysis to further study the core molecular pathways that regulate the wound healing ability of hADSCs. hADSCs isolated from DM patients or cultured in medium containing AGEs in vitro exhibited decreased effectiveness in stem cell therapy. The expression of miRNA-1248 was decreased in the hADSCs of DM patients and hence failed to positively regulate stem cell activity, differentiation functions, and angiogenesis promotion effect. This concomitantly increased the expression of CITED2, an inhibitor of HIF-1α, thus influencing growth factors that promote angiogenesis, cellular proliferation, and wound healing. Overall, our data demonstrated that the glucolipotoxicity-impaired wound healing ability of hADSCs might occur through the miR-1248/CITED2/HIF-1α pathway. MiRNA-1248 may have potential to be used as a novel therapeutic target for wound healing in DM patients or restoring the wound healing ability of diabetic hADSCs.
登录
查看更多内容
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
胰岛素下调转录核心调节因子 CITED2（内皮细胞中促血管生成功能的抑制剂）
影响因子：
7.7
作者：
Wang, Xuanchun;Lockhart, Samuel M.;Rask-Madsen, Christian
通讯作者：
Rask-Madsen, Christian
用自体细胞外基质/基质血管成分凝胶治疗人类慢性伤口：一项符合 STROBE 标准的研究
影响因子：
1.6
作者：
Deng C;Wang L;Feng J;Lu F
通讯作者：
Lu F
影响因子：
2.9
作者：
Cianfarani, Francesca;Toietta, Gabriele;Odorisio, Teresa
通讯作者：
Odorisio, Teresa
影响因子：
8.1
作者：
Kim M;Neinast MD;Frank AP;Sun K;Park J;Zehr JA;Vishvanath L;Morselli E;Amelotte M;Palmer BF;Gupta RK;Scherer PE;Clegg DJ
通讯作者：
Clegg DJ