TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I

Wang, Hui; Wang, Lin; Li, Song; Zhang, Yan-Wan; Ye, Jue; Xu, Rui‐Xia; Shi, Na; Meng, Xia

doi:10.1590/s0100-879x2013005002515

Cited by 2 publications

(6 citation statements)

References 22 publications

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“…Our previous data showed that overexpression of human TNNI3K promoted mouse embryonic stem cell differentiation into beating cardiomyocytes 20 . Moreover, overexpression of rat Tnni3k increased cardiac contractile function of ventricular myocytes in adult rats by enhancing phosphorylation of cardiac troponin I, indicating that TNNI3K enhanced cardiac function 21 . Additionally, Lai et al reported that intramyocardial administration of TNNI3K ‐overexpressed P19CL6 cells improved cardiac performance in mice with MI compared to the control group 23 .…”

Section: Discussionmentioning

confidence: 97%

“…20 Moreover, overexpression of rat Tnni3k increased cardiac contractile function of ventricular myocytes in adult rats by enhancing phosphorylation of cardiac troponin I, indicating that TNNI3K enhanced cardiac function. 21 Additionally, Lai et al reported that intramyocardial administration of TNNI3Koverexpressed P19CL6 cells improved cardiac performance in mice with MI compared to the control group. 23 However, Tang et al found that transgenic DBA/2 J mice overexpressing human TNNI3K demonstrated a more rapid decline in fractional shortening in a left ventricular pressure overload model compared with non-transgenic controls, suggesting that TNNI3K accelerated cardiomyopathy progression after surgery.…”

Section: Tnni3k-cko Promotes Myocardial Apoptosismentioning

confidence: 99%

“…Our previous data showed that the overexpression of cardiac‐specific TNNI3K promoted differentiation of mouse embryonic stem cells into cardiomyocytes 20 . In adult rats, TNNI3K overexpression increased the contractile function of ventricular myocytes 21 . Moreover, overexpression of human TNNI3K enhanced cardiac function in transgenic mice 22 .…”

Section: Introductionmentioning

confidence: 99%

“…20 In adult rats, TNNI3K overexpression increased the contractile function of ventricular myocytes. 21 Moreover, overexpression of human TNNI3K enhanced cardiac function in transgenic mice. 22 TNNI3K also promoted the myogenesis of P19CL6-derived cardiomyocytes, protected the myocardium from ischaemic injury and enhanced cardiac performance.…”

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confidence: 99%

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Knockout of cardiac troponin I‐interacting kinase leads to cardiac dysfunction and remodelling

Zhang

et al. 2022

Clin Exp Pharma Physio

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Cardiac troponin I-interacting kinase (TNNI3K) is a cardiac-specific kinase that has been identified as a diagnostic marker and a therapeutic target in cardiovascular diseases. However, the biological function of TNNI3K in cardiac dysfunction and remodelling remains elusive. In the present study, a Tnni3k cardiomyocyte-specific knockout (Tnni3k-cKO) mouse model was established. Echocardiography was used to evaluate cardiac function in mice. Heart failure markers were detected using enzyme-linked immunosorbent assay. Haematoxylin and eosin staining, wheat germ agglutinin staining, Masson's trichrome staining, Sirius red staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining were used to assess histopathological changes, cardiac hypertrophy, collagen deposition and myocardial apoptosis, respectively. Expression levels of TNNI3K, apoptosis-related proteins, and p38 mitogen-activated protein kinase were measured using Western blot analysis. Compared to wild-type controls, cardiac dysfunction and cardiac remodelling of Tnni3k-cKO mice increased gradually with age. Tnni3k-cKO mice exhibited cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. Upregulation of cleaved caspase-3 in Tnni3k-cKO mice appeared to be related to phosphorylation and activation of the p38 mitogen-activated protein kinase signalling pathway. In conclusion, this study shows that TNNI3K is essential for cardiac development and function, providing new insights into the development of novel therapeutic strategies for cardiac diseases.

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Section: Discussionmentioning

confidence: 97%

Section: Tnni3k-cko Promotes Myocardial Apoptosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Knockout of cardiac troponin I‐interacting kinase leads to cardiac dysfunction and remodelling

Zhang

et al. 2022

Clin Exp Pharma Physio

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“…33 In vivo, TNNI3K protein is located at the cardiac sarcomeric Z-disc, 32 where it modulates contractile function. 32,33 Multiple QTL mapping studies for different cardiac traits have identified this locus, and ultimately, this gene, to be responsible for the observed phenotypic variation observed across inbred strains of mice. 16,18,[34][35][36] This convergence of seemingly distinct cardiac phenotypes on this single gene is likely attributable to 3 factors.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Troponin I–Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation

et al. 2023

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Background: Identifying genetic variants which impact the level of cell cycle reentry and establishing the degree of cell cycle progression in those variants could help guide development of therapeutic interventions aimed at effecting cardiac regeneration. We observed that C57Bl6/NCR (B6N) mice have a marked increase in cardiomyocyte S-phase activity following permanent coronary artery ligation as compared to infarcted DBA/2J (D2J) mice. Methods: Cardiomyocyte cell cycle activity post-infarction was monitored in D2J, (D2J x B6N)-F1 and [(D2J x B6N)-F1 x D2J] backcross mice via bromodeoxyuridine or 5-ethynyl-2' -deoxyuridine incorporation, using a nuclear-localized transgenic reporter to identify cardiomyocyte nuclei. Genome-wide quantitative trait locus (QTL) analysis, fine scale genetic mapping, whole exome sequencing and RNA-seq analyses of the backcross mice were performed to identify the gene responsible for the elevated cardiomyocyte S-phase phenotype. Results: (D2J x B6N)-F1 mice exhibited a 14-fold increase in cardiomyocyte S-phase activity in ventricular regions remote from infarct scar as compared to D2J mice (0.798 ± 0.09% vs. 0.056 ± 0.004%; p < 0.001). QTL analysis of [(D2J x B6N)-F1 x D2J] backcross mice revealed that the gene responsible for differential S-phase activity was located on the distal arm of Chromosome 3 (LOD score = 6.38; p < 0.001). Additional genetic and molecular analyses identified 3 potential candidates. Of these, troponin I-interacting kinase ( Tnni3k ) is expressed in B6N hearts but not in D2J hearts. Transgenic expression of Tnni3k in a D2J genetic background results in elevated cardiomyocyte S-phase activity post-injury. Cardiomyocyte S-phase activity in both TNNI3K-expressing and TNNI3K-nonexpressing mice results in the formation of polyploid nuclei. Conclusions: These data indicate that TNNI3K expression increases the level of cardiomyocyte S-phase activity following injury.

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TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I

Cited by 2 publications

References 22 publications

Knockout of cardiac troponin I‐interacting kinase leads to cardiac dysfunction and remodelling

Knockout of cardiac troponin I‐interacting kinase leads to cardiac dysfunction and remodelling

Cardiac Troponin I–Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation

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