Adipose tissue-derived stem cells ameliorate hyperglycemia, insulin resistance and liver fibrosis in the type 2 diabetic rats.
Adipose tissue-derived stem cells ameliorate hyperglycemia, insulin resistance and liver fibrosis in the type 2 diabetic rats.
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DOI：
10.1186/s13287-017-0743-7
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发表时间：
2017-12-19
影响因子：
7.5
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Liao N;Zheng Y;Xie H;Zhao B;Zeng Y;Liu X;Liu J
2型糖尿病（T2 D）与肝纤维化密切相关，但目前尚无有效的治疗方法。本研究旨在探讨脂肪干细胞对2型糖尿病大鼠胰岛素抵抗、高血糖和肝纤维化的治疗作用。我们首先通过使用高脂饮食（HFD）、低剂量链脲佐菌素（STZ）和四氯化碳（CCl 4）的组合建立了具有肝纤维化的T2 D大鼠模型。随后，分别通过尾静脉注射PBS或ADSC对模型大鼠进行给药。此后，分别通过生化分析、ELISA、组织病理学检查和q-PCR测定来评估胰岛素抵抗和肝功能。进一步分析ADSCs对TGF-β1/SMAD 3信号通路影响的分子机制。我们的数据显示，ADSC移植显著减轻了肝损伤T2 D大鼠的胰岛素抵抗和高血糖。ADSC移植可通过改善肝功能、抑制肝纤维化病理改变、下调TGF-β1和磷酸化SMAD 3等途径减轻肝损伤。这些结果提示ADSC移植可通过抑制TGF-β1/SMAD 3信号通路改善胰岛素抵抗、高血糖和肝纤维化，这可能为T2 D肝纤维化的治疗提供一种潜在的策略。本文的在线版本（doi：10.1186/s13287-017-0743-7）包含补充材料，可供授权用户使用。
Type 2 diabetes (T2D) is closely associated with liver fibrosis, but no effective treatments are currently available. This study was designed to investigate the therapeutic effects of ADSCs on insulin resistance, hyperglycemia, and liver fibrosis on T2D rats. We first established a T2D rat model with liver fibrosis by using the combination of a high-fat diet (HFD), low-dose streptozotocin (STZ), and carbon tetrachloride (CCl4). Subsequently, the model rats were administrated by tail vein injection of PBS or ADSCs, respectively. Thereafter, insulin resistance and liver function were assessed by biochemical analysis, ELISA, histopathological examination, and q-PCR assay, respectively. Moreover, the molecular mechanisms of ADSCs on the effect of the TGF-β1/SMAD3 signaling pathway were further analyzed. Our data showed that ADSC transplantation significantly alleviated insulin resistance and hyperglycemia in the liver-injured T2D rats. We also found that ADSC transplantation could attenuate liver injury by improving liver function and inhibiting pathological changes of liver fibrosis, as well as through downregulation of TGF-β1 and phosphorylated SMAD3 both in vitro and in vivo. These findings suggested that ADSC transplantation can ameliorate insulin resistance, hyperglycemia, and liver fibrosis via suppressing TGF-β1/SMAD3 signaling, which may provide a potential treatment strategy for liver fibrosis of T2D. The online version of this article (doi:10.1186/s13287-017-0743-7) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Niu L;Cui X;Qi Y;Xie D;Wu Q;Chen X;Ge J;Liu Z
通讯作者：
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影响因子：
4.6
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Liao N;Wu M;Pan F;Lin J;Li Z;Zhang D;Wang Y;Zheng Y;Peng J;Liu X;Liu J
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影响因子：
3.3
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通讯作者：
Chiou, Tzyy-Wen
影响因子：
2
作者：
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通讯作者：
Yan, Shengli
影响因子：
4.6
作者：
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通讯作者：
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