Overexpressing HPGDS in adipose-derived mesenchymal stem cells reduces inflammatory state and improves wound healing in type 2 diabetic mice.
Overexpressing HPGDS in adipose-derived mesenchymal stem cells reduces inflammatory state and improves wound healing in type 2 diabetic mice.
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脂肪间充质干细胞中过度表达 HPGDS 可减少 2 型糖尿病小鼠的炎症状态并改善伤口愈合
DOI：
10.1186/s13287-022-03082-w
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发表时间：
2022-08-03
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
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作者：
在糖尿病患者中，伤口愈合延迟被认为是促炎细胞和因子过度募集和滞留的结果。从糖尿病人足部皮肤差异表达基因中鉴定出造血前列腺素D合成酶(HPGDS)。HPGDS负责炎症介质前列腺素D2(PGD2)的产生。因此，我们旨在探讨HPGDS是否可以作为糖尿病伤口(DW)的治疗靶点。在这项研究中，我们比较了基因表达总库中糖尿病人足部皮肤和非糖尿病人足部皮肤的基因表达谱。我们检测了糖尿病小鼠创面免疫成分的特点，并探讨了差异表达的Hpgds在糖尿病创面愈合中的作用及其机制。在活体研究中，我们设计了过表达Hpgds的ADSC(ADSCHpgds)，并使用全层皮肤伤口模型评估了其对糖尿病伤口愈合的影响。在体外研究中，我们评估了ADSCHpgds条件培养液和PGD2对内毒素(LPS)诱导的巨噬细胞的作用。Hpgds在2型糖尿病小鼠创面中表达显著下调，其缺失延迟了正常创面的愈合。ADSCHpgds通过减少中性粒细胞和CD8T细胞募集，促进M2巨噬细胞极化，增加生长因子的产生，加速DW的愈合。ADSCHpgds条件培养液对M2巨噬细胞转化的促进作用明显优于单纯ADSC条件培养液。结果表明，Hpgds是小鼠创面愈合所必需的，ADSCHpgds通过改善小鼠创面的抗炎状态，使创面愈合的增殖期趋于正常，从而促进创面愈合。这些发现为糖尿病创面的治疗策略提供了新的见解。网上版载有补充材料，可在10.1186/s13287-022-03082-w查阅。
In diabetes, delayed wound healing was considered as the result of excessive recruitment and retention of pro-inflammatory cells and factors. Hematopoietic prostaglandin D synthase (HPGDS) was identified from differently expressed genes of diabetic human foot skin. HPGDS is responsible for the production of prostaglandin D2 (PGD2), an inflammatory mediator. Therefore, we aim to explore whether HPGDS could be a therapeutic target in the diabetic wound (DW). In this study, we compared gene expression profilings of diabetic human foot skin and non-diabetic human foot skin from the Gene Expression Omnibus database. We detected the characteristics of immune components in diabetic mice wound and investigated the role and underlying mechanism of the differently expressed Hpgds for the diabetic wound healing. For in vivo studies, we engineered ADSC to overexpress Hpgds (ADSCHpgds) and evaluated its effects on diabetic wound healing using a full-thickness skin wound model. For in vitro studies, we evaluated the role of ADSCHpgds conditioned medium and PGD2 on Lipopolysaccharide (LPS) induced macrophage. Hpgds was significantly down-regulated in type 2 diabetic mice wound and its deficiency delayed normal wound healing. ADSCHpgds accelerated DW healing by reducing neutrophil and CD8T cell recruitment, promoting M2 macrophage polarization and increasing the production of growth factors. ADSCHpgds conditioned medium showed superior capability in promoting M2 macrophage transition than conditioned medium derived from ADSC alone. Our results demonstrated that Hpgds is required for wound healing, and ADSCHpgds could accelerate DW healing by improving anti-inflammatory state and normalizing the proliferation phase of wound healing in mice. These findings provide a new insight in the therapeutic strategy of diabetic wound. The online version contains supplementary material available at 10.1186/s13287-022-03082-w.
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影响因子：
5.2
作者：
Everett E;Mathioudakis N
通讯作者：
Mathioudakis N
影响因子：
4.3
作者：
Aydin F;Kaya A;Karapinar L;Kumbaraci M;Imerci A;Karapinar H;Karakuzu C;Incesu M
通讯作者：
Incesu M
DOI：
10.1158/1078-0432.ccr-08-2649
发表时间：
2009-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Landskroner-Eiger S;Qian B;Muise ES;Nawrocki AR;Berger JP;Fine EJ;Koba W;Deng Y;Pollard JW;Scherer PE
通讯作者：
Scherer PE
影响因子：
4.6
作者：
Cheng, Biao;Liu, Hong-Wei;Sheng, Zhi-Yong
通讯作者：
Sheng, Zhi-Yong
影响因子：
5.9
作者：
Shokouh P;Jeppesen PB;Hermansen K;Laustsen C;Stødkilde-Jørgensen H;Hamilton-Dutoit SJ;Søndergaard Schmedes M;Qi H;Stokholm Nørlinger T;Gregersen S
通讯作者：
Gregersen S