Polycystin-1 mitigates damage and regulates CTGF expression through AKT activation during cardiac ischemia/reperfusion

Aránguiz, Pablo; Romero, Pablo; Vásquez, F; Flores-Vergara, Raúl; Aravena, Diego; Pecchi, Gina; González, Marı́a Julieta; Olmedo, Ivonne; Pedrozo, Zully

doi:10.1016/j.bbadis.2020.165986

Cited by 8 publications

(10 citation statements)

References 43 publications

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“…However, independent of the presence of cilia, cardiomyocyte-specific knockdown of PC1 promotes cardiomyocyte alterations [ 16 , 40 ] that are distinct from the ones elicited by Polycystin-2 knockdown [ 37 ]. Moreover, we previously showed that NRVM knockdown to PC1 did not change the PC2 expression [ 41 ] as well as cardiomyocytes-restricted silencing of PC1 mice model [ 16 ], suggesting that our results are not influenced by PC2 alterations. Altogether, this evidence suggests that these proteins play different roles in cardiomyocytes, so we did not explore the role of Polycystin-2 in IGF-1-induced cardiomyocyte hypertrophy.…”

Section: Discussionmentioning

confidence: 53%

“…A possible mechanism through PC1 regulates PTP1B activity could involved AKT as a negative modulator of this phosphatase. PC1 stimulates AKT activity [ 41 , 44 ], while PTP1B phosphorylation on Ser(50) by AKT negatively regulates the activity of this phosphatase [ 45 ]. Future experiments should address this hypothesis andinvestigate a potential interaction between PTP1B and PC1 with the IGF-1R and whether PC1 regulates PTP1B availability to clarify the mechanism involved in this signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

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Polycystin-1 is required for insulin-like growth factor 1-induced cardiomyocyte hypertrophy

et al. 2021

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Cardiac hypertrophy is the result of responses to various physiological or pathological stimuli. Recently, we showed that polycystin-1 participates in cardiomyocyte hypertrophy elicited by pressure overload and mechanical stress. Interestingly, polycystin-1 knockdown does not affect phenylephrine-induced cardiomyocyte hypertrophy, suggesting that the effects of polycystin-1 are stimulus-dependent. In this study, we aimed to identify the role of polycystin-1 in insulin-like growth factor-1 (IGF-1) signaling in cardiomyocytes. Polycystin-1 knockdown completely blunted IGF-1-induced cardiomyocyte hypertrophy. We then investigated the molecular mechanism underlying this result. We found that polycystin-1 silencing impaired the activation of the IGF-1 receptor, Akt, and ERK1/2 elicited by IGF-1. Remarkably, IGF-1-induced IGF-1 receptor, Akt, and ERK1/2 phosphorylations were restored when protein tyrosine phosphatase 1B was inhibited, suggesting that polycystin-1 knockdown deregulates this phosphatase in cardiomyocytes. Moreover, protein tyrosine phosphatase 1B inhibition also restored IGF-1-dependent cardiomyocyte hypertrophy in polycystin-1-deficient cells. Our findings provide the first evidence that polycystin-1 regulates IGF-1-induced cardiomyocyte hypertrophy through a mechanism involving protein tyrosine phosphatase 1B.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Polycystin-1 is required for insulin-like growth factor 1-induced cardiomyocyte hypertrophy

et al. 2021

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“…PC1 is a critical modulator of apoptosis and fibrosis. Cardiomyocyte PC1 plays a pivotal role in regulating fibroblast-to-myofibroblast differentiation, with implications for cardiac fibrosis and remodeling [111]. Also noteworthy is the fact that mice harboring a cardiomyocyte-selective conditional silencing of PC1 do not develop fibrosis after being subjected to transverse aortic constriction [108], supporting the role of this protein in cardiac remodeling.…”

Section: The Heart In Adpkdmentioning

confidence: 99%

“…Also noteworthy is the fact that mice harboring a cardiomyocyte-selective conditional silencing of PC1 do not develop fibrosis after being subjected to transverse aortic constriction [108], supporting the role of this protein in cardiac remodeling. Moreover, PC1 mitigates cardiac damage during ischemia/reperfusion, likely through AKT activation, and regulates the connective tissue growth factor expression in cardiomyocytes [111]. The cardiomyocyte-specific deletion of PKD1 impairs the systolic and diastolic functions in mice [112].…”

Section: The Heart In Adpkdmentioning

confidence: 99%

Cardiac Involvement in Autosomal Dominant Polycystic Kidney Disease

2021

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Cardiovascular disorders are the main complication in autosomal dominant polycystic kidney disease (ADPKD). contributing to both morbidity and mortality. This review considers clinical studies unveiling cardiovascular features in patients with ADPKD. Additionally, it focuses on basic science studies addressing the dysfunction of the polycystin proteins located in the cardiovascular system as a contributing factor to cardiovascular abnormalities. In particular, the effects of polycystin proteins’ deficiency on the cardiomyocyte function have been considered.

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“…In the heart, CTGF mediates CF proliferation, migration, and adhesion (Kemp et al, 2004), CF-to-MF differentiation during cardiac fibrosis (Frazier et al, 1996), and CM hypertrophy (Hayata et al, 2008;Panek et al, 2009). Both CM and CF express and release CTGF in response to various stimuli including mechanical stretch, ROS, Ang II, TGF-β, and IR (Blom et al, 2002;Ahmed et al, 2004;Matsui and Sadoshima, 2004;Shakil Ahmed et al, 2011;Dorn et al, 2018;Zhao et al, 2019;Zhuang et al, 2019;Long et al, 2020;Aránguiz et al, 2021). Various signaling pathways are involved in CTGF upregulation, including SMAD, protein kinase C (PKC), ROS, RhoA, c-Jun NH2-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K), and ERK (Matsui and Sadoshima, 2004).…”

Section: Connective Tissue Growth Factormentioning

confidence: 99%

Communication Between Cardiomyocytes and Fibroblasts During Cardiac Ischemia/Reperfusion and Remodeling: Roles of TGF-β, CTGF, the Renin Angiotensin Axis, and Non-coding RNA Molecules

et al. 2021

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Communication between cells is a foundational concept for understanding the physiology and pathology of biological systems. Paracrine/autocrine signaling, direct cell-to-cell interplay, and extracellular matrix interactions are three types of cell communication that regulate responses to different stimuli. In the heart, cardiomyocytes, fibroblasts, and endothelial cells interact to form the cardiac tissue. Under pathological conditions, such as myocardial infarction, humoral factors released by these cells may induce tissue damage or protection, depending on the type and concentration of molecules secreted. Cardiac remodeling is also mediated by the factors secreted by cardiomyocytes and fibroblasts that are involved in the extensive reciprocal interactions between these cells. Identifying the molecules and cellular signal pathways implicated in these processes will be crucial for creating effective tissue-preserving treatments during or after reperfusion. Numerous therapies to protect cardiac tissue from reperfusion-induced injury have been explored, and ample pre-clinical research has attempted to identify drugs or techniques to mitigate cardiac damage. However, despite great success in animal models, it has not been possible to completely translate these cardioprotective effects to human applications. This review provides a current summary of the principal molecules, pathways, and mechanisms underlying cardiomyocyte and cardiac fibroblast crosstalk during ischemia/reperfusion injury. We also discuss pre-clinical molecules proposed as treatments for myocardial infarction and provide a clinical perspective on these potential therapeutic agents.

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Polycystin-1 mitigates damage and regulates CTGF expression through AKT activation during cardiac ischemia/reperfusion

Cited by 8 publications

References 43 publications

Polycystin-1 is required for insulin-like growth factor 1-induced cardiomyocyte hypertrophy

Polycystin-1 is required for insulin-like growth factor 1-induced cardiomyocyte hypertrophy

Cardiac Involvement in Autosomal Dominant Polycystic Kidney Disease

Communication Between Cardiomyocytes and Fibroblasts During Cardiac Ischemia/Reperfusion and Remodeling: Roles of TGF-β, CTGF, the Renin Angiotensin Axis, and Non-coding RNA Molecules

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