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Role and mechanism of RGS14 in improving acute myocardial infarction by inhibiting TAK1 activation

Published on Mar. 05, 2026Total Views: 24 timesTotal Downloads: 9 timesDownloadMobile

Author: WU Qinghua 1, 2 DUAN Shaofeng 2, 3 TAN Chongyuan 2, 3 ZHANG Lirong 2, 3 ZHANG Jiaxing 2, 3 HU Yufeng 2, 3 SHE Zhigang 1, 2, 3 LI Hongliang 1, 2, 3

Affiliation: 1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China 2. State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Ganzhou 341000, Jiangxi Province, China 3. Gannan Innovation and Translational Medicine Research Institute, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China

Keywords: Regulator of G-protein signaling 14 Acute myocardial infarction Inflammation Apoptosis TAK1

DOI: 10.12173/j.issn.1004-5511.202511095

Reference: Wu QH, Duan SF, Tan CY, et al. Role and mechanism of RGS14 in improving acute myocardial infarction by inhibiting TAK1 activation[J]. Yixue Xinzhi Zazhi, 2026, 36(2): 169-178. DOI: 10.12173/j.issn.1004-5511.202511095. [Article in Chinese]

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Abstract

Objective  This study aims to investigate the role and mechanism of regulator of G-protein signaling 14 (RGS14) protein in acute myocardial infarction (AMI).

Methods  The RGS14 knockout mice were selected to construct AMI model. The cardiac tissue and serum of mice were collected 24 h after modeling, the degree of inflammatory infiltration in the cardiac tissue was analyzed by immunohistochemical analysis, and biochemical analyzer detects serum biochemical indicators. Overexpression and knockdown adenovirus were constructed in vitro and transfected into primary rat cardiomyocytes. RT-qPCR and Western blot were used to detect the expression of RGS14, inflammation and apoptosis related markers mRNA and protein. TUNEL staining was used to analyze the apoptosis of heart tissue.

Results  The expression of RGS14 in myocardial cells of AMI model mouse was downregulated. Compared with wild-type mice, RGS14 knockout mice exhibited increased AMI induced cardiac dysfunction, inflammatory response, and apoptosis. Conversely, overexpression of RGS14 inhibited cardiomyocyte apoptosis in vitro. The protective effect of RGS14 on AMI injury is closely related to its inhibition of TAK1-JNK/p38 signaling pathway activation. Inhibition of TAK1 alleviates the adverse effects of RGS14 knockdown on AMI in vitro.

Conclusion  RGS14 exerts a protective function in the process of inflammation and apoptosis after AMI, and alleviates cardiac dysfunction by inhibiting the activation of TAK1, which provides a new potential for the treatment of AMI.

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References

1.Yap J, Irei J, Lozano-Gerona J, et al. Macrophages in cardiac remodelling after myocardial infarction[J]. Nat Rev Cardiol, 2023, 20(6): 373-385.

2.Zhang Q, Wang L, Wang S, et al. Signaling pathways and targeted therapy for myocardial infarction[J]. Signal Transduct Target Ther, 2022, 7(1): 78.

3.Prabhu SD, Frangogiannis NG. The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis[J]. Circ Res, 2016, 119(1): 91-112.

4.Zurek M, Johansson E, Palmer M, et al. Neuregulin-1 induces cardiac hypertrophy and impairs cardiac performance in post-myocardial infarction rats[J]. Circulation, 2020, 142(13): 1308-1311.

5.Li J, Zhang Y, Li C, et al. HSPA12B attenuates cardiac dysfunction and remodelling after myocardial infarction through an eNOS-dependent mechanism[J]. Cardiovasc Res, 2013, 99(4): 674-684.

6.Zhou X, Zhang C, Wu X, et al. Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction[J]. Nat Commun, 2022, 13(1): 6672.

7.Saito Y, Oyama K, Tsujita K, et al. Treatment strategies of acute myocardial infarction: updates on revascularization, pharmacological therapy, and beyond[J]. J Cardiol, 2023, 81(2): 168-178.

8.董丹,孙艳秋,燕燕. 中国居民2002-2021年急性心肌梗死死亡趋势年龄-时期-队列模型分析[J]. 数理医药学杂志, 2023, 36(10): 721-726. [Dong D, Sun YQ, Yan Y. Acute myocardial infarction mortality among Chinese residents from 2002 to 2021:an age-period-cohort model analysis[J]. Journal of Mathematical Medicine, 2023, 36(10): 721-726.]

9.Koelle MR. A new family of G-protein regulators—the RGS proteins[J]. Curr Opin Cell Biol, 1997, 9(2): 143-147.

10.Watson N, Linder ME, Druey KM, et al. RGS family members: GTPase-activating proteins for heterotrimeric G-protein α-subunits[J]. Nature, 1996, 383(6596): 172-175.

11.Zhang P, Mende U. Regulators of G-protein signaling in the heart and their potential as therapeutic targets[J]. Circ Res, 2011, 109(3): 320-333.

12.胡哲夫,唐其柱. RGS与心血管系统的研究进展[J]. 医学研究杂志, 2018, 47(11): 7-10. [Hu ZF, Tang QZ. Advances in research on RGS and the cardiovascular system[J]. Journal of Medical Research, 2018, 47(11): 7-10.]

13.Romero M, Jiménez R, Toral M, et al. Vascular and central activation of peroxisome proliferator-activated receptor-attenuates angiotensin II-induced hypertension: role of RGS-5.[J]. J Pharmacol Exp Ther, 2016, 358(1): 151-163.

14.Evans PR, Lee SE, Smith Y, et al. Postnatal developmental expression of regulator of G protein signaling 14 (RGS14) in the mouse brain[J]. J Comp Neurol, 2014, 522(1): 186-203.

15.Zhang JK, Ding MJ, Liu H, et al. Regulator of G-protein signaling 14 protects the liver from ischemia-reperfusion injury by suppressing TGF-β-activated kinase 1 activation[J]. Hepatology, 2022, 75(2): 338-352.

16.Li Y, Tang X, Li X, et al. Regulator of G protein signalling 14 attenuates cardiac remodelling through the MEK-ERK1/2 signalling pathway[J]. Basic Res Cardiol, 2016, 111(4): 47.

17.Percie du Sert N, Hurst V, Ahluwalia A, et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research[J]. Br J Pharmacol, 2020, 177(16): 3617-3624.

18.Bao MW, Cai Z, Zhang XJ, et al. Dickkopf-3 protects against cardiac dysfunction and ventricular remodelling following myocardial infarction[J]. Basic Res Cardiol, 2015, 110(3): 25.

19.Harbin NH, Bramlett SN, Montanez-Miranda C, et al. RGS14 regulation of post-synaptic signaling and spine plasticity in brain[J]. Int J Mol Sci, 2021, 22(13): 6823.

20.Hatanpaa KJ, Raisanen JM, Herndon E, et al. Hippocampal sclerosis in dementia, epilepsy, and ischemic injury: differential vulnerability of hippocampal subfields[J]. J Neuropathol Exp Neurol, 2014, 73(2): 136-142.

21.Wu X, Iroegbu CD, Peng J, et al. Cell death and exosomes regulation after myocardial infarction and ischemia-reperfusion[J]. Front Cell Dev Biol, 2021, 9: 673677.

22.Meeran MFN, Azimullah S, Adeghate E, et al. Nootkatone attenuates myocardial oxidative damage, inflammation, and apoptosis in isoproterenol-induced myocardial infarction in rats[J]. Phytomedicine, 2021, 84: 153405.

23.Dhingra R, Rabinovich-Nikitin I, Rothman S, et al. Proteasomal degradation of TRAF2 mediates mitochondrial dysfunction in doxorubicin-cardiomyopathy[J]. Circulation, 2022, 146(12): 934-954.

24.Li HL, Zhuo ML, Wang D, et al. Targeted cardiac overexpression of A20 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction[J]. Circulation, 2007, 115(14): 1885-1894.

25.Sohn WJ, Ji YR, Kim HS, et al. Rgs19 regulates mouse palatal fusion by modulating cell proliferation and apoptosis in the MEE[J]. Mech Dev, 2012, 129(9-12): 244-254.

26.Huang J, Stewart A, Maity B, et al. RGS6 suppresses Ras-induced cellular transformation by facilitating Tip60-mediated Dnmt1 degradation and promoting apoptosis[J]. Oncogene, 2014, 33(27): 3604-3611.

27.Wang Z, Huang HE, He W, et al. Regulator of G-protein signaling 5 protects cardiomyocytes against apoptosis during in vitro cardiac ischemia-reperfusion in mice by inhibiting both JNK1/2 and P38 signaling pathways[J]. Biochem Biophys Res Commun, 2016, 473(2): 551-557.

28.黄会慧,蔡永祥,都欢,等. 水凝胶调控巨噬细胞促进心肌梗死后心肌修复的研究进展[J]. 医学新知, 2024, 34(5): 572-581. [Huang HH, Cai YX, Dou H, et al. Hydrogel modulate macrophages to promote myocardial repair after myocardial infarction[J]. Yixue Xinzhi Zazhi, 2024, 34(5): 572-581.]

29.Cai S, Zhao M, Zhou B, et al. Mitochondrial dysfunction in macrophages promotes inflammation and suppresses repair after myocardial infarction[J]. J Clin Invest, 2023, 133(4): e159498.

30.Wang X, Guo Z, Ding Z, et al. Inflammation, autophagy, and apoptosis after myocardial infarction[J]. J Am Heart Assoc, 2018, 7(9): e008024.

31.Jung M, Dodsworth M, Thum T. Inflammatory cells and their non-coding RNAs as targets for treating myocardial infarction[J]. Basic Res Cardiol, 2019, 114(1): 4.

32.Wang L, Zhang X, Lin ZB, et al. Tripartite motif 16 ameliorates nonalcoholic steatohepatitis by promoting the degradation of phospho-TAK1[J]. Cell Metab, 2021, 33(7): 1372-1388. e7.

33.Bai B, Ji Z, Wang F, et al. CTRP12 ameliorates post-myocardial infarction heart failure through down-regulation of cardiac apoptosis, oxidative stress and inflammation by influencing the TAK1-p38 MAPK/JNK pathway[J]. Inflamm Res, 2023, 72(7): 1375-1390.

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