Myeloid MKL1 Disseminates Cues to Promote Cardiac Hypertrophy in Mice

Abstract

Cardiac hypertrophy is a key pathophysiological process in the heart in response to stress cues. Although taking place in cardiomyocytes, the hypertrophic response is influenced by other cell types, both within the heart and derived from circulation. In the present study we investigated the myeloid-specific role of megakaryocytic leukemia 1 (MKL1) in cardiac hypertrophy. Following transverse aortic constriction (TAC), myeloid MKL1 conditional knockout (MFCKO) mice exhibit an attenuated phenotype of cardiac hypertrophy compared to the WT mice. In accordance, the MFCKO mice were protected from excessive cardiac inflammation and fibrosis as opposed to the WT mice. Conditioned media collected from macrophages enhanced the pro-hypertrophic response in cardiomyocytes exposed to endothelin in an MKL1-dependent manner. Of interest, expression levels of macrophage derived miR-155, known to promote cardiac hypertrophy, were down-regulated in the MFCKO mice compared to the WT mice. MKL1 depletion or inhibition repressed miR-155 expression in macrophages. Mechanistically, MKL1 interacted with NF-κB to activate miR-155 transcription in macrophages. In conclusion, our data suggest that MKL1 may contribute to pathological hypertrophy via regulating macrophage-derived miR-155 transcription.

Epigenetic Repression of Chloride Channel Accessory 2 Transcription in Cardiac Fibroblast: Implication in Cardiac Fibrosis

“…The mice were maintained in an SPF environment with 12 h light/dark cycles and libitum access to food and water. Cardiac fibrosis was induced by permanent ligation of left-anterior descending (LAD) coronary artery or transverse aortic constriction (TAC) as previously described ( Yang et al, 2017 ; Liu et al, 2021b , c ).…”

“…Transient transfection was performed with Lipofectamine 2000. Cells were harvested 48 h after transfection and reporter activity was measured using a luciferase reporter assay system (Promega) as previously described ( Kong et al, 2021a , c ; Liu et al, 2021c ; Zhang et al, 2021 ). MS-275 and MC-1568 were purchased from Selleck.…”

A GSK3-SRF Axis Mediates Angiotensin II Induced Endothelin Transcription in Vascular Endothelial Cells

“…RNA was extracted with the RNeasy RNA isolation kit (Qiagen, Hilden, Germany). Reverse transcriptase reactions were performed using a SuperScript First-strand Synthesis System (Invitrogen, Waltham, MA, United States) as previously described ( Zhang et al, 2020 ; Liu et al, 2021 ). Real-time PCR reactions were performed on an ABI Prism 7500 system with the following primers: ET1 , 5′-AGAGTGTGTCTACTTCTGCCA-3′ and 5′-CTTCCAAGTCCATACGGAACAA-3′; GSK3B, 5′-GG CAGCATGAAAGTTAGCAGA-3′ and 5′-GGCGACCAGT TCTCCTGAATC-3′.…”

A KDM4-DBC1-SIRT1 Axis Contributes to TGF-b Induced Mesenchymal Transition of Intestinal Epithelial Cells

“…Small interfering RNAs were purchased from Dharmacon. Transient transfections were performed with Lipofectamine 2000 as previously described ( Chen et al, 2021 ; Kong et al, 2021b ; Liu et al, 2021a , b ; Zhang et al, 2021 ).…”