Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy

Yang, Lei; Li, Yutian; Wang, Xiaohong; Mu, Xingjiang; Qin, Dongze; Huang, Wei; Alshahrani, Saeed; Nieman, Michelle L.; Peng, Jiangtong; Essandoh, Kobina; Peng, Tianqing; Wang, Yigang; Lorenz, John N.; Soleimani, Manoocher; Zhao, Zhi‐Qing; Fan, Guo-Chang

doi:10.1074/jbc.m116.715805

Cited by 44 publications

(53 citation statements)

References 47 publications

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“…Given that IGF-1R is a critical regulator of physiologic hypertrophy, we sought to determine the expression profile of these endosomal-associated genes during physiologic cardiac hypertrophy. Mice (FVB/N background) were subjected to treadmill training for inducing physiologic cardiac hypertrophy, as we previously described (24). There was a significant increase in the ratio of HW:BW of treadmilltrained mice compared with sedentary control, confirming that the model was successfully generated (Fig.…”

Section: Expression Profiles Of Endosome-associated Genes In Treadmilsupporting

confidence: 52%

“…Following acclimatization, mice underwent intense exercise training at 10 m/min for 5 min + an increase of 1 m/min every minute up to 25 m/min to induce cardiac hypertrophy. Mice were trained daily for 1 h or until mice were tired and unresponsive to shock stimuli for 10 s, as we previously described (24). Heart samples were collected after a 1-wk training period.…”

Section: Physiologic Hypertrophy Model Of Treadmill Exercise Trainingmentioning

confidence: 99%

“…Mouse heart sections (5 mm in thickness) were produced from tissues and stained with Masson's Trichrome 2000 Kit (American MasterTech, Lodi, CA, USA) and PicroSirius Red Staining Kit (Thermo Fisher Scientific, Waltham, MA, USA) according to the manufacturers' protocols. To analyze individual cardiomyocyte size, heart sections were stained with wheat germ agglutinin (WGA) as we previously described (24). Images were taken under the microscope (Inteslight; Nikon, Tokyo, Japan), and the imageprocessing program ImageJ (NIH) was used to analyze cell sizes.…”

Section: Cardiac Histologymentioning

confidence: 99%

“…Plasma membrane proteins were isolated using the Minute Plasma Membrane Protein Isolation Kit (Invent Biotechnologies, Plymouth, MN, USA) according to the manufacturer's protocol. Samples (10-100 mg) were subjected to SDS-PAGE as described in detail by Yang et al (24). The dilutions and sources of the primary antibodies used in this study are as follows: rabbit anti-IGF-1R (1:1000; MilliporeSigma); mouse anti-Tsg101 (1:1000; Santa Cruz Biotechnology, Dallas, TX, USA); mouse anti-Akt (total Akt) (1:1000; Santa Cruz Biotechnology), rabbit anti-pAkt-Ser473 (1:1000; Santa Cruz Biotechnology); rabbit anti-FIP3 (1:500; Santa Cruz Biotechnology); rabbit anti-pAkt-Thr308 (1:500; Cell Signaling Technology, Danvers, MA, USA); rabbit anti-Rab7 (1:500; Cell Signaling Technology); rabbit anti-Rab4a (1:500; Proteintech, Rosemont, IL, USA); rabbit anti-Rab5a (1:500; Proteintech); rabbit anti-Rab11a (1:500; Proteintech); rabbit anti-periostin (1:500; Santa Cruz Biotechnology); and mouse antia-actin (1:1000; MilliporeSigma).…”

Section: Western Blotting Assaysmentioning

confidence: 99%

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Tsg101 positively regulates physiologic‐like cardiac hypertrophy through FIP3‐mediated endosomal recycling of IGF‐1R

et al. 2019

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Development of physiologic cardiac hypertrophy has primarily been ascribed to the IGF‐1 and its receptor, IGF‐1 receptor (IGF‐1R), and subsequent activation of the protein kinase B (Akt) pathway. However, regulation of endosome‐mediated recycling and degradation of IGF‐1R during physiologic hypertrophy has not been investigated. In a physiologic hypertrophy model of treadmill‐exercised mice, we observed that levels of tumor susceptibility gene 101 (Tsg101), a key member of the endosomal sorting complex required for transport, were dramatically elevated in the heart compared with sedentary controls. To determine the role of Tsg101 on physiologic hypertrophy, we generated a transgenic (TG) mouse model with cardiac‐specific overexpression of Tsg101. These TG mice exhibited a physiologic‐like cardiac hypertrophy phenotype at 8 wk evidenced by: 1) the absence of cardiac fibrosis, 2) significant improvement of cardiac function, and 3) increased total and plasma membrane levels of IGF‐1R and increased phosphorylation of Akt. Mechanistically, we identified that Tsg101 interacted with family‐interacting protein 3 (FIP3) and IGF‐1R, thereby stabilizing FIP3 and enhancing recycling of IGF‐1R. In vitro, adenovirus‐mediated overexpression of Tsg101 in neonatal rat cardiomyocytes resulted in cell hypertrophy, which was blocked by addition of monensin, an inhibitor of endosome‐mediated recycling, and by small interfering RNA—mediated knockdown (KD) of FIP3. Furthermore, cardiac‐specific KD of Tsg101 showed a significant reduction in levels of endosomal recycling compartment members (Rabila and FIP3), IGF‐1R, and Akt phosphorylation. Most interestingly, Tsg101‐KD mice failed to develop cardiac hypertrophy after intense treadmill training. Taken together, our data identify Tsg101 as a novel positive regulator of physiologic cardiac hypertrophy through facilitating the FIP3‐mediated endosomal recycling of IGF‐1R.—Essandoh, K., Deng, S., Wang, X., Jiang, M., Mu, X., Peng, J., Li, Y., Peng, T., Wagner, K.‐U., Rubinstein, J., Fan, G.‐C. Tsg101 positively regulates physiologic‐like cardiac hypertrophy through FIP3‐mediated endosomal recycling of IGF‐1R. FASEB J. 33, 7451–7466 (2019). http://www.fasebj.org

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Section: Expression Profiles Of Endosome-associated Genes In Treadmilsupporting

confidence: 52%

Section: Physiologic Hypertrophy Model Of Treadmill Exercise Trainingmentioning

confidence: 99%

Section: Cardiac Histologymentioning

confidence: 99%

Section: Western Blotting Assaysmentioning

confidence: 99%

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Tsg101 positively regulates physiologic‐like cardiac hypertrophy through FIP3‐mediated endosomal recycling of IGF‐1R

et al. 2019

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“…Growing studies demonstrate that miRNAs play an important role in the progression of cardiac hypertrophy and even heart failure [14–16]. Recently, miR-497 is up-regulated in cardiac hypertrophy and heart failure and is identified as a novel regulator of cardiac hypertrophy [9].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-497 Inhibits Cardiac Hypertrophy by Targeting Sirt4

et al. 2016

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Cardiac hypertrophy is an adaptive enlargement of the myocardium in response to overload pressure of heart. From abundant studies, a conclusion is drawn that many microRNAs (miRNAs) are associated with cardiac hypertrophy and heart failure. To investigate the role of microRNA-497 (miR-497) in myocardial hypertrophy, two models were established in this study from cell level to integral level. Cardiac hypertrophy was induced by using angiotensin Ⅱ (Ang Ⅱ) in vitro and was created by transverse abdominal aortic constriction (TAC) in vivo. There was a significant decrease expression of miR-497 in cardiac hypertrophy models. Moreover, overexpression of miR-497 inhibited myocardial hypertrophy both in vitro and in vivo without heart function variation. In addition, luciferase reporter assays demonstrated that Sirt4 was a direct target gene of miR-497. Taking together, our study indicates that miR-497 modulates cardiac hypertrophy by targeting Sirt4 and may serve as a potential therapeutic substance in the course.

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Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?

Nijholt

Sánchez-Aguilera

Voorrips

et al. 2022

European J of Heart Fail

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Impaired exercise capacity is the key symptom of heart failure (HF) and is associated with reduced quality of life and higher mortality rates. Unfortunately, current therapies, although generally lifesaving, have only small or marginal effects on exercise capacity. Specific strategies to alleviate exercise intolerance may improve quality of life, while possibly improving prognosis as well. There is overwhelming evidence that physical exercise improves performance in cardiac and skeletal muscles in health and disease. Unravelling the mechanistic underpinnings of exercise-induced improvements in muscle function could provide targets that will allow us to boost exercise performance in HF. With the current review we discuss: (i) recently discovered signalling pathways that govern physiological muscle growth as well as mitochondrial quality control mechanisms that underlie metabolic adaptations to exercise; (ii) the mechanistic underpinnings of exercise intolerance in HF and the benefits of exercise in HF patients on molecular, functional and prognostic levels; and (iii) potential molecular therapeutics to improve exercise performance in HF. We propose that novel molecular therapies to boost adaptive muscle growth and mitochondrial quality control in HF should always be combined with some form of exercise training.

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Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy

Cited by 44 publications

References 47 publications

Tsg101 positively regulates physiologic‐like cardiac hypertrophy through FIP3‐mediated endosomal recycling of IGF‐1R

Tsg101 positively regulates physiologic‐like cardiac hypertrophy through FIP3‐mediated endosomal recycling of IGF‐1R

MicroRNA-497 Inhibits Cardiac Hypertrophy by Targeting Sirt4

Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?

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