Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway
Cardiorenal syndrome type 3 (CRS-3) is damage to the heart following acute kidney injury (AKI). Although many experiments have found that inflammation, oxidative stress, and cardiomyocyte death are involved in cardiomyocyte pathophysiological alterations during CRS-3, they lack a non-bias analysis t...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.630412/full |
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| author | Jin Wang Xuefeng Sun Xu Wang Shaoyuan Cui Ran Liu Jiaona Liu Bo Fu Ming Gong Conghui Wang Yushen Shi Qianqian Chen Guangyan Cai Xiangmei Chen |
| author_facet | Jin Wang Xuefeng Sun Xu Wang Shaoyuan Cui Ran Liu Jiaona Liu Bo Fu Ming Gong Conghui Wang Yushen Shi Qianqian Chen Guangyan Cai Xiangmei Chen |
| author_sort | Jin Wang |
| collection | DOAJ |
| description | Cardiorenal syndrome type 3 (CRS-3) is damage to the heart following acute kidney injury (AKI). Although many experiments have found that inflammation, oxidative stress, and cardiomyocyte death are involved in cardiomyocyte pathophysiological alterations during CRS-3, they lack a non-bias analysis to figure out the primary mediator of cardiac dysfunction. Herein proteomic analysis was operated in CRS-3 and growth factor receptor-bound protein 2 (Grb2) was identified as a regulator involving AKI-related myocardial damage. Increased Grb2 was associated with cardiac diastolic dysfunction and mitochondrial bioenergetics impairment; these pathological changes could be reversed through the administration of a Grb2-specific inhibitor during AKI. Molecular investigation illustrated that augmented Grb2 promoted cardiomyocyte mitochondrial metabolism disorder through inhibiting the Akt/mTOR signaling pathway. Besides that, Mouse Inflammation Array Q1 further identified IL-6 as the upstream stimulator of Grb2 upregulation after AKI. Exogenous administration of IL-6 induced cardiomyocyte damage and mitochondrial bioenergetics impairment, whereas these effects were nullified in cardiomyocytes pretreated with Grb2 inhibitor. Our results altogether identify CRS-3 to be caused by the upregulations of IL-6/Grb2 which contribute to cardiac dysfunction through inhibiting the Akt/mTOR signaling pathway and inducing cardiomyocyte mitochondrial bioenergetics impairment. This finding provides a potential target for the clinical treatment of patients with CRS-3. |
| first_indexed | 2024-04-11T22:33:22Z |
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| id | doaj.art-d16ce7daeaf14c9c9a84cdf4f0331eb9 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T22:33:22Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-d16ce7daeaf14c9c9a84cdf4f0331eb92022-12-22T03:59:18ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-03-01910.3389/fcell.2021.630412630412Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR PathwayJin WangXuefeng SunXu WangShaoyuan CuiRan LiuJiaona LiuBo FuMing GongConghui WangYushen ShiQianqian ChenGuangyan CaiXiangmei ChenCardiorenal syndrome type 3 (CRS-3) is damage to the heart following acute kidney injury (AKI). Although many experiments have found that inflammation, oxidative stress, and cardiomyocyte death are involved in cardiomyocyte pathophysiological alterations during CRS-3, they lack a non-bias analysis to figure out the primary mediator of cardiac dysfunction. Herein proteomic analysis was operated in CRS-3 and growth factor receptor-bound protein 2 (Grb2) was identified as a regulator involving AKI-related myocardial damage. Increased Grb2 was associated with cardiac diastolic dysfunction and mitochondrial bioenergetics impairment; these pathological changes could be reversed through the administration of a Grb2-specific inhibitor during AKI. Molecular investigation illustrated that augmented Grb2 promoted cardiomyocyte mitochondrial metabolism disorder through inhibiting the Akt/mTOR signaling pathway. Besides that, Mouse Inflammation Array Q1 further identified IL-6 as the upstream stimulator of Grb2 upregulation after AKI. Exogenous administration of IL-6 induced cardiomyocyte damage and mitochondrial bioenergetics impairment, whereas these effects were nullified in cardiomyocytes pretreated with Grb2 inhibitor. Our results altogether identify CRS-3 to be caused by the upregulations of IL-6/Grb2 which contribute to cardiac dysfunction through inhibiting the Akt/mTOR signaling pathway and inducing cardiomyocyte mitochondrial bioenergetics impairment. This finding provides a potential target for the clinical treatment of patients with CRS-3.https://www.frontiersin.org/articles/10.3389/fcell.2021.630412/fullCRS-3GRB2cardiomyocyteskidneymitochondria |
| spellingShingle | Jin Wang Xuefeng Sun Xu Wang Shaoyuan Cui Ran Liu Jiaona Liu Bo Fu Ming Gong Conghui Wang Yushen Shi Qianqian Chen Guangyan Cai Xiangmei Chen Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway Frontiers in Cell and Developmental Biology CRS-3 GRB2 cardiomyocytes kidney mitochondria |
| title | Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway |
| title_full | Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway |
| title_fullStr | Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway |
| title_full_unstemmed | Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway |
| title_short | Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway |
| title_sort | grb2 induces cardiorenal syndrome type 3 roles of il 6 cardiomyocyte bioenergetics and akt mtor pathway |
| topic | CRS-3 GRB2 cardiomyocytes kidney mitochondria |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.630412/full |
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