Diabetes induces fibrotic changes in the lung through the activation of TGF-β signaling pathways.
Diabetes induces fibrotic changes in the lung through the activation of TGF-β signaling pathways.
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DOI：
10.1038/s41598-018-30449-y
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发表时间：
2018-08-09
影响因子：
4.6
通讯作者：
Ravindra PV
中科院分区：
文献类型：
--
作者：
Talakatta G;Sarikhani M;Muhamed J;Dhanya K;Somashekar BS;Mahesh PA;Sundaresan N;Ravindra PV
从长远来看，糖尿病会严重影响多个器官，如肾脏、心脏、大脑、肝脏和眼睛。这些重要器官功能的逐渐丧失会导致死亡。然而，糖尿病对肺组织的影响尚不清楚。我们研究的临床和实验数据表明，糖尿病会引起肺部的炎症和纤维化变化。这些变化是由TGF-β激活的上皮-间质转化（EMT）信号通路介导的。我们的研究还发现，葡萄糖限制促进了间充质到上皮的转化（MET），并显著逆转了炎症和纤维化的变化，这表明糖尿病诱导的EMT部分是由高血糖介导的。此外，糖尿病细胞持续暴露于高葡萄糖浓度（25 mM）下，可促进caveolin-1、N-cadherin、SIRT3、SIRT7和乳酸水平上调，提示长期糖尿病可能促进细胞增殖。综上所述，我们的研究结果首次证明糖尿病通过TGF-β1激活的EMT途径诱导肺纤维化变化，并且在糖尿病的初始阶段，升高的SMAD7部分保护肺。这些发现对糖尿病患者的管理具有启示意义。
In the long term, diabetes profoundly affects multiple organs, such as the kidney, heart, brain, liver, and eyes. The gradual loss of function in these vital organs contributes to mortality. Nonetheless, the effects of diabetes on the lung tissue are not well understood. Clinical and experimental data from our studies revealed that diabetes induces inflammatory and fibrotic changes in the lung. These changes were mediated by TGF-β-activated epithelial-to-mesenchymal transition (EMT) signaling pathways. Our studies also found that glucose restriction promoted mesenchymal-to-epithelial transition (MET) and substantially reversed inflammatory and fibrotic changes, suggesting that diabetes-induced EMT was mediated in part by the effects of hyperglycemia. Additionally, the persistent exposure of diabetic cells to high glucose concentrations (25 mM) promoted the upregulation of caveolin-1, N-cadherin, SIRT3, SIRT7 and lactate levels, suggesting that long-term diabetes may promote cell proliferation. Taken together, our results demonstrate for the first time that diabetes induces fibrotic changes in the lung via TGF-β1-activated EMT pathways and that elevated SMAD7 partially protects the lung during the initial stages of diabetes. These findings have implications for the management of patients with diabetes.
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影响因子：
8.4
作者：
Lee, Jung-Yun;Jeon, Inpyo;Park, Sang Min
通讯作者：
Park, Sang Min
影响因子：
2.6
作者：
Boussadia, O;Kutsch, S;Kemler, R
通讯作者：
Kemler, R
影响因子：
2.6
作者：
Hu, Yuxin;Ma, Zhongsen;Yang, Junling
通讯作者：
Yang, Junling
糖尿病微血管疾病和肺纤维化：血小板和全身炎症的贡献。
影响因子：
5.6
作者：
Jagadapillai R;Rane MJ;Lin X;Roberts AM;Hoyle GW;Cai L;Gozal E
通讯作者：
Gozal E
影响因子：
4.8
作者：
Miao, Feng;Wu, Xiwei;Natarajan, Rama
通讯作者：
Natarajan, Rama