Linagliptin, A Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor, Ameliorates Experimental Autoimmune Myocarditis.
Linagliptin, A Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor, Ameliorates Experimental Autoimmune Myocarditis.
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Linagliptin 是一种基于黄嘌呤的二肽基肽酶 4 抑制剂，可改善实验性自身免疫性心肌炎。
DOI：
10.1016/j.jacbts.2021.04.006
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Sasano T
中科院分区：
文献类型：
--
作者：
Shiheido-Watanabe Y;Maejima Y;Kasama T;Tamura N;Nakagama S;Ito Y;Hirao K;Isobe M;Sasano T
利格列汀（一种DPP-4抑制剂）治疗不仅可以缓解EAM，还可以缓解ICIM。DPP-4与组织蛋白酶G物理相互作用并增强其活性。利格列汀促进SerpinA3N活性，从而抑制组织蛋白酶G活性。组织蛋白酶G通过上调血管紧张素II加重EAM。利格列汀抑制EAM心脏的氧化应激。本研究旨在揭示如何通过给予二肽基肽酶(DPP)-4抑制剂利格列汀改善实验性自身免疫性心肌炎（EAM）的机制。利格列汀治疗后，rar相关孤儿核受体γ阳性Th17细胞浸润至EAM心肌的数量明显减少。基于串联质谱的分析表明，DPP-4在EAM心脏中与组织蛋白酶G结合，从而通过抑制SerpinA3N活性来保护组织蛋白酶G活性。利格列汀也能抑制EAM心脏的氧化应激。因此，我们发现DPP-4通过与组织蛋白酶G相互作用在EAM的进展中起不利作用，而组织蛋白酶G反过来又抑制SerpinA3N的活性。
Treatment with linagliptin, a DPP-4 inhibitor, alleviates not only EAM but also ICIM. DPP-4 physically interacts with cathepsin G and enhances its activity. Linagliptin promotes SerpinA3N activity, thereby suppressing cathepsin G activity. Cathepsin G aggravates EAM through upregulating angiotensin II. Linagliptin suppresses oxidative stress in EAM hearts. This study sought to show the mechanism of how to ameliorate experimental autoimmune myocarditis (EAM) by administering dipeptidyl peptidase (DPP)-4 inhibitor linagliptin. The number of RAR-related orphan nuclear receptor gamma–positive Th17 cells infiltrated to the EAM myocardium was significantly attenuated by linagliptin treatment. Tandem mass spectrometry–based analysis demonstrated that DPP-4 binds to cathepsin G in EAM hearts, thereby protecting cathepsin G activity through inhibiting SerpinA3N activity. Linagliptin suppresses oxidative stress in EAM hearts as well. Thus, we found that DPP-4 plays a detrimental role in the progression of EAM by interacting with cathepsin G, which, in turn, suppresses SerpinA3N activity.
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DOI：
10.1016/s1470-2045(18)30608-9
发表时间：
2018-12
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Salem JE;Manouchehri A;Moey M;Lebrun-Vignes B;Bastarache L;Pariente A;Gobert A;Spano JP;Balko JM;Bonaca MP;Roden DM;Johnson DB;Moslehi JJ
通讯作者：
Moslehi JJ
影响因子：
120.7
作者：
Rosenstock, Julio;Perkovic, Vlado;Coles, Adrian
通讯作者：
Coles, Adrian
影响因子：
158.5
作者：
Scirica, Benjamin M.;Bhatt, Deepak L.;Simmons, D.
通讯作者：
Simmons, D.
影响因子：
4.8
作者：
Horvath, AJ;Irving, JA;Whisstock, JC
通讯作者：
Whisstock, JC
影响因子：
4.4
作者：
Richter, R;Bistrian, R;Forssmann, U
通讯作者：
Forssmann, U