IGF1 Knockdown Hinders Myocardial Development through Energy Metabolism Dysfunction Caused by ROS-Dependent FOXO Activation in the Chicken Heart

Abstract

Insulin-like growth factor 1 (IGF1) is a multifunctional cellular regulatory factor that can regulate cell growth and development by mediating growth hormone stimulation. However, the mechanism of IGF1 dysfunction in cardiomyocyte development is seldom reported. To study this, we employed the models of IGF1 knockdown in chicken embryo in vivo and in cardiomyocytes in vitro. We detected the antioxidant capacity, PI3K/Akt pathway, energy metabolism-related genes, and myocardial development-related genes. Our results revealed that the low expression of IGF1 can significantly suppress the antioxidant capacity and increase the ROS (P<0.05) levels, activating the AMPK and PI3K pathway by inhibiting the expression of IRS1. We also found that myocardial energy metabolism is blocked through IGF1, GLUT, and IGFBP inhibition, further inducing myocardial developmental disorder by inhibiting Mesp1, GATA, Nkx2.5, and MyoD expression. Altogether, we conclude that low IGF1 expression can hinder myocardial development through the dysfunction of energy metabolism caused by ROS-dependent FOXO activation.

The effect of Co-Q10 on allergic rhinitis and allergic asthma

“…Disruption of Nrf2 also leads to eosinophils increases in lung tissues, airway remodeling, AHR, goblet cell hyperplasia, and level of Th2 cytokines. The Nrf2 signaling plays an essential role in broncho-protection [ 22 ]. In our study, Co-Q10 treatment can increased Nrf2 expression and significantly enhanced Nrf2 gene activation.…”

“…ARDS may be suppressed by controlling of inflammation and cell damage by increasing anti-inflammatory and antioxidant factors. Co-Q10 supplementation with other anti-COVID-19 drugs, might be beneficial on patients with ARDS [ 22 , 25 ]. Moreover, two interactional factors, oxidative stress and inflammation involve in ARDS and activation of Nrf2 can control oxidative stress and inflammation in ARDS [ 22 ].…”

“…Co-Q10 supplementation with other anti-COVID-19 drugs, might be beneficial on patients with ARDS [ 22 , 25 ]. Moreover, two interactional factors, oxidative stress and inflammation involve in ARDS and activation of Nrf2 can control oxidative stress and inflammation in ARDS [ 22 ]. Therefore, Nrf2 activation with Co-Q10 and other treatments can be effective drug in control and treatment of ADRS in COVID-19.…”

Exosomes: Potential Player in Endothelial Dysfunction in Cardiovascular Disease

“…Downstream activated AKT of exosome containing HMGB can also lead to inflammation in ECs via the mTORC1/4EBP1/P70S6K pathway [ 49 ]. In addition, in another pathway induced by AKT, the FOXO1 molecule can induce inflammation in ECs by activating the NF-Kβ transcription factor [ 50 , 51 ]. Downstream activated GSK3β of this exosome can also activate the TCF transcription factor via the β-Catenin/APC/Axin/CK pathway, which translates IL-1β gene to produce the cytokine; subsequently it generates inflammation [ 52 ].…”

Identifying functional genes and pathways towards a unifying model for atrial fibrillation

“…PIK3R1 encodes for a subunit of PIK3, which is critical in insulin resistance 15 , and in the regulation of myogenic differentiation, myoblast proliferation, and myotube hypertrophy 16,17 . The PI3K-Akt signaling pathway is activated by insulin like growth factor-1 (IGF-1) 17 which is critical in regulation of energy metabolism in cardiomyocytes 18 , and decreases autophagy and apoptosis [19][20][21][22] . Inhibition of the PI3K-Akt signaling in the heart is thought to contribute to AF in patients on ibrutinib 23 , an immunotherapeutic agent that acts as a Bruton's tyrosine kinase inhibitor 24 .…”