The combined inhibition of the CaMKIIδ and calcineurin signaling cascade attenuates IGF‐IIR‐induced cardiac hypertrophy

Chen, Chung‐Hao; Lin, Jingwei; Huang, Kevin Chih-Yang; Yeh, Yu Lan; Shen, Chia-Yao; Badrealam, Khan Farheen; Ho, Tsung‐Jung; Padma, Viswanadha Vijaya; Kuo, Wei‐Wen; Huang, Chih‐Yang

doi:10.1002/jcp.29242

Cited by 16 publications

(14 citation statements)

References 26 publications

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“…A previous study revealed that treatment with KN-93 (a CaMKII inhibitor) significantly reduced the expression of CH-related proteins, including NFATc3, p-HDAC4, p-HDAC5, GATA-4, and the hypertrophy marker BNP. Furthermore, the combined inhibition of the CaMKII and CaN signaling pathways may obviously relieve CH responses [ 13 ]. The results of the current study revealed that siCaMKII inhibited protein expression in the CaMKII pathway and further reduced that in the CnA-NFAT signal pathway, thereby improving Ang II-induced hypertrophic cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

“…The constitutive activation of CaN and its downstream target, NFAT, are thought to play an important role in abnormal CH [ 11 , 12 ]. Moreover, it is known that CaMKII phosphorylates many vital signaling factors that are related to initiating abnormal hypertrophy [ 13 ]. Transgenic overexpression of the splice variants CaMKII δ b (located in the nucleus) and CaMKII δ c (located in the cytosol) promotes CH and dilated cardiomyopathy, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Cardiac CaMKIIδ and Wenxin Keli Prevents Ang II‐Induced Cardiomyocyte Hypertrophy by Modulating CnA‐NFATc4 and Inflammatory Signaling Pathways in H9c2 Cells

Chen

Xing

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Previous studies have demonstrated that calcium-/calmodulin-dependent protein kinase II (CaMKII) and calcineurin A-nuclear factor of activated T-cell (CnA-NFAT) signaling pathways play key roles in cardiac hypertrophy (CH). However, the interaction between CaMKII and CnA-NFAT signaling remains unclear. H9c2 cells were cultured and treated with angiotensin II (Ang II) with or without silenced CaMKIIδ (siCaMKII) and cyclosporine A (CsA, a calcineurin inhibitor) and subsequently treated with Wenxin Keli (WXKL). Patch clamp recording was conducted to assess L-type Ca2+ current (ICa-L), and the expression of proteins involved in signaling pathways was measured by western blotting. Myocardial cytoskeletal protein and nuclear translocation of target proteins were assessed by immunofluorescence. The results indicated that siCaMKII suppressed Ang II-induced CH, as evidenced by reduced cell surface area and ICa-L. Notably, siCaMKII inhibited Ang II-induced activation of CnA and NFATc4 nuclear transfer. Inflammatory signaling was inhibited by siCaMKII and WXKL. Interestingly, CsA inhibited CnA-NFAT pathway expression but activated CaMKII signaling. In conclusion, siCaMKII may improve CH, possibly by blocking CnA-NFAT and MyD88 signaling, and WXKL has a similar effect. These data suggest that inhibiting CaMKII, but not CnA, may be a promising approach to attenuate CH and arrhythmia progression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cardiac CaMKIIδ and Wenxin Keli Prevents Ang II‐Induced Cardiomyocyte Hypertrophy by Modulating CnA‐NFATc4 and Inflammatory Signaling Pathways in H9c2 Cells

Chen

Xing

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…47 Calcineurin is serine/threonine protein phosphatase regulated by CaMKII, which plays an important role in the regulation of pathological hypertrophy. 48 Calcineurin could reciprocal repress with miR-133 to regulate cardiac hypertrophy. 49 Jiang et al 50…”

Section: Lncrnas Controls the Function Of Calcium Channelsmentioning

confidence: 99%

“… 46 Lnc‐H19 as the precursor of miR‐675, which inhibit the expression of CaMKIIδ, is a negative regulator of cardiomyocyte hypertrophy (Figure 2). 47 Calcineurin is serine/threonine protein phosphatase regulated by CaMKII, which plays an important role in the regulation of pathological hypertrophy 48 . Calcineurin could reciprocal repress with miR‐133 to regulate cardiac hypertrophy 49 .…”

Section: Lncrnas In Regulation Of Pathophysiological Process Of Cardimentioning

confidence: 99%

LncRNAs in cardiac hypertrophy: From basic science to clinical application

Liu

Zhang

2020

J Cellular Molecular Medi

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“…Our previous researches demonstrate that signaling mechanism involving insulin-like growth factor II receptor (IGFIIR), a fetal gene, is key in the pathological progression of hypertrophy [ 9 , 10 ]. Reactivation of IGFIIR signaling in the heart during stresses leads to cardiac hypertrophy and heart failure.…”

Section: Introductionmentioning

confidence: 99%

IGF IIRα-triggered pathological manifestations in the heart aggravate renal inflammation in STZ-induced type-I diabetes rats

Lin

Paul

Kuo

et al. 2021

Aging

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Pathological manifestations in either heart or kidney impact the function of the other and form the basis for the development of cardiorenal syndrome. However, the mechanism or factors involved in such scenario are not completely elucidated. In our study, to find the correlation between late fetal gene expression in diabetic hearts and their influence on diabetic nephropathy, we created a rat model with cardiac specific overexpression of IGF-IIRα, which is an alternative splicing variant of IGFIIR, expressed in pathological hearts. In this study, transgenic rats over expressing cardiac specific IGF-IIRα and non-transgenic animal models established in SD rats were administered with single dose of streptozotocin (STZ, 55 mg/Kg) to induce Type I diabetes. The correlation between IGF-IIRα and kidney damages were further determined based on their intensity of damage in the kidneys. The results show that cardiac specific overexpression of IGF-IIRα elevates the diabetes associated inflammation and morphological changes in the kidneys. The diabetic transgenic rats showed advancement in the pathological features such a renal tubular damage, collagen accumulation and enhancement in STAT3 associated mechanism of renal fibrosis. The results therefore show that that IGF-IIRα expression in the heart during pathological condition may worsen symptoms of diabetic nephropathy in rats.

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The combined inhibition of the CaMKIIδ and calcineurin signaling cascade attenuates IGF‐IIR‐induced cardiac hypertrophy

Cited by 16 publications

References 26 publications

Cardiac CaMKIIδ and Wenxin Keli Prevents Ang II‐Induced Cardiomyocyte Hypertrophy by Modulating CnA‐NFATc4 and Inflammatory Signaling Pathways in H9c2 Cells

Cardiac CaMKIIδ and Wenxin Keli Prevents Ang II‐Induced Cardiomyocyte Hypertrophy by Modulating CnA‐NFATc4 and Inflammatory Signaling Pathways in H9c2 Cells

LncRNAs in cardiac hypertrophy: From basic science to clinical application

IGF IIRα-triggered pathological manifestations in the heart aggravate renal inflammation in STZ-induced type-I diabetes rats

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