Abstract：Myosin light chain kinase (MYLK) 3 gene is a member of the MYLK family, which is mainly expressed in myocardial tissue. Its protein product, cardiac MYLK, plays an important role in cardiac development, cardiac contraction, and sarcomeric tissue formation. When its expression is reduced or absent, it can affect myocardial formation and development, leads to congenital heart disease, heart hypertrophy, dilated heart disease, and other heart diseases. The discovery of MYLK3 gene makes the clinical further understanding of heart diseases from the gene level, which may provide a new theoretical basis and therapeutic target for the diagnosis and treatment of heart diseases. This article reviews the structure and function of MYLK3 gene and its research progress in heart disease.
曾婧 刘晓阳 白杨 王大维▲. 肌球蛋白轻链激酶3基因在心脏疾病中的研究进展[J]. 中国医药导报, 2022, 19(33): 63-65,87.
ZENG Jing LIU Xiaoyang BAI Yang WANG Dawei▲. Research progress of myosin light chain kinase 3 gene in heart disease. 中国医药导报, 2022, 19(33): 63-65,87.
[1] Seguchi O，Takashima S，Yamazaki S，et al. A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart [J]. J Clin Invest，2007，117（10）：2812-2824.
[2] Kamm KE，Stull JT. Signaling to myosin regulatory light chain in sarcomeres [J]. J Biol Chem，2011，286（12）：9941- 9947.
[3] Phelps DL，Borley JV，Flower KJ，et al. Methylation of MYLK3 gene promoter region：a biomarker to stratify surgical care in ovarian cancer in a multicentre study [J]. Br J Cancer，2017，116（10）：1287-1293.
[4] Luo XL，Zhang P，Liu X，et al. Myosin light chain 2 marks differentiating ventricular cardiomyocytes derived from human embryonic stem cells [J]. Pflugers Arch，2021，473（7）：991-1007.
[5] Kamikubo K，Tsukamoto O，Uyama-Saito Y，et al. Non-Radioactive In Vitro Cardiac Myosin Light Chain Kinase Assays [J]. J Vis Exp，2020，2020（160）：e61168.
[6] X Cai L，Tanada Y，D Bello G，et al. Cardiac MLC2 kinase is localized to the Z-disc and interacts with α-actinin2 [J]. Sci Rep，2019，9（1）：12580.
[7] Taniguchi M，Okamoto R，Ito M，et al. New Isoform of Cardiac Myosin Light Chain Kinase and the Role of Cardiac Myosin Phosphorylation in alpha1-Adrenoceptor Mediated Inotropic Response [J]. PLoS One，2015，10（10）：e141130.
[8] Hodatsu A，Fujino N，Uyama Y，et al. Impact of cardiac myosin light chain kinase gene mutation on development of dilated cardiomyopathy [J]. ESC Heart Fail，2019，6（2）：406-415.
[9] Chan JY，Takeda M，Briggs LE，et al. Identification of cardiac-specific myosin light chain kinase [J]. Circ Res，2008，102（5）：571-580.
[10] Hu S，Cheng M，Guo X，et al. Down-regulation of miR-200c attenuates AngⅡ-induced cardiac hypertrophy via targeting the MLCK-mediated pathway [J]. J Cell Mol Med，2019，23（4）：2505-2516.
[11] 姚欣雨，李奉瑾，乔梦茹，等.胎儿先天性心脏病遗传学病因的研究进展[J].国际妇产科学杂志，2022，49（1）：77-81.
[12] 许文婧，魏莉莉，王莹，等.我国围生儿先天性心脏病发病率的Meta分析[J].国际生殖健康/计划生育杂志，2020，39（4）：269-275.
[13] Dixit R，Narasimhan C，Balekundri VI，et al. Functional analysis of novel genetic variants of NKX2-5 associated with nonsyndromic congenital heart disease [J]. Am J Med Genet A，2021，185（12）：3644-3663.
[14] Kang HY，Choi YK，Jeung EB. Inhibitory effect of progesterone during early embryonic development：Suppression of myocardial differentiation and calcium-related transcriptome by progesterone in mESCs：Progesterone disturb cardiac differentiation of mESCs through lower cytosolic Ca2+ [J]. Reprod Toxicol，2016，64（6）：169-179.
[15] Lee JH，Yoo YM，Jung EM，et al. Inhibitory effect of octyl- phenol and bisphenol A on calcium signaling in cardiomyocyte differentiation of mouse embryonic stem cells [J]. J Physiol Pharmacol，2019，70（3）：435-442.
[16] Islam YF，Joseph R，Chowdhury RR，et al. Heart Failure Induced by Perinatal Ablation of Cardiac Myosin Light Chain Kinase [J]. Front Physiol，2016，7：480.
[17] 李若冰，张国刚，徐锴，等.扩张型心肌病运动康复治疗的研究进展[J].中华老年心脑血管病杂志，2021，23（6）：661-663.
[18] Tobita T，Nomura S，Morita H，et al. Identification of MYLK3 mutations in familial dilated cardiomyopathy [J]. Sci Rep，2017，7（1）：17495.
[19] Tougas CL，Grindrod T，Cai LX，et al. Heterozygous Mylk3 Knockout Mice Partially Recapitulate Human DCM With Heterozygous MYLK3 Mutations [J]. Front Physiol，2019， 10：696.
[20] Pagliaro BR，Cannata F，Stefanini GG，et al. Myocardial ischemia and coronary disease in heart failure [J]. Heart Fail Rev，2020，25（1）：53-65.
[21] Min KD，Asakura M，Liao Y，et al. Identification of genes related to heart failure using global gene expression profiling of human failing myocardium [J]. Biochem Biophys Res Commun，2010，393（1）：55-60.
[22] Aalikhani M，Alikhani M，Shamsabadi F，et al. In silico drug repurposing for the treatment of heart diseases using gene expression data and molecular docking techniques [J]. Biochem Biophys Res Commun，2021，572（7）：138-144.
[23] Oldfield CJ，Duhamel TA，Dhalla NS. Mechanisms for the transition from physiological to pathological cardiac hypertrophy [J]. Can J Physiol Pharmacol，2020，98（2）：74-84.
[24] 何铭垣，葛俊峰，黄玲，等.心肌型肌球蛋白轻链激酶调控肌球蛋白轻链对心肌肥大的影响[J].中华全科医学，2021，19（8）：1257-1261，1402.
[25] Nakamura M，Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy [J]. Nat Rev Cardiol，2018，15（7）：387-407.
[26] 杨楠，李雪萍，宋梅，等.MLCK在慢性心力衰竭中作用机制的研究[J].医学信息，2021，34（8）：60-63.
[27] Carey RM，Whelton PK. New findings bearing on the prevention，detection and management of high blood pressure [J]. Curr Opin Cardiol，2021，36（4）：429-435.
[28] Warren SA，Briggs LE，Zeng H，et al. Myosin light chain phosphorylation is critical for adaptation to cardiac stress [J]. Circulation，2012，126（22）：2575-2588.
[29] Gao L，Zheng YJ，Gu SS，et al. Degradation of cardiac myosin light chain kinase by matrix metalloproteinase-2 contributes to myocardial contractile dysfunction during ischemia/reperfusion [J]. J Mol Cell Cardiol，2014，77（10）：102-112.
[30] Jen■a D，Melenovsk?伥 V，Stehlik J，et al. Heart failure after myocardial infarction：incidence and predictors [J]. ESC Heart Fail，2021，8（1）：222-237.
[31] Gu X，Liu X，Xu D，et al. Cardiac functional improvement in rats with myocardial infarction by up-regulating cardiac myosin light chain kinase with neuregulin [J]. Cardiovasc Res，2010，88（2）：334-343.
[32] Williams JL，Paudyal A，Awad S，et al. Mylk3 null C57BL/ 6N mice develop cardiomyopathy，whereas Nnt null C57BL/ 6J mice do not [J]. Life Sci Alliance，2020，3（4）：e00593.
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