ATF3 in atherosclerosis: a controversial transcription factor
AbstractAtherosclerosis, the pathophysiological basis of most malignant cardiovascular diseases, remains a global concern. Transcription factors play a key role in regulating cell function and disease progression in developmental signaling pathways involved in atherosclerosis. Activated transcription factor (ATF) 3 is an adaptive response gene in the ATF/cAMP response element binding (CREB) protein family that acts as a transcription suppressor or activator by forming homodimers or heterodimers with other ATF/CREB members. Appropriate ATF3 expression is vital for normal physiological cell function. Notably, ATF3 exhibits d...
Source: Journal of Molecular Medicine - October 8, 2022 Category: Molecular Biology Source Type: research
I536T variant of RBM20 affects splicing of cardiac structural proteins that are causative for developing dilated cardiomyopathy
AbstractRBM20 is one of the genes predisposing to dilated cardiomyopathy (DCM). Variants in the RS domain have been reported in many DCM patients, but the pathogenicity of variants within the RNA-recognition motif remains unknown. Two human patients with the I536T-RBM20 variant without an apparent DCM phenotype were identified in sudden death cohorts. A splicing reporter assay was performed, and an I538T knock-in mouse model (Rbm20I538T) was generated to determine the significance of this variant. The reporter assay demonstrated that the human I536T variant affected theTTN splicing pattern compared to wild-type. In the mou...
Source: Journal of Molecular Medicine - October 5, 2022 Category: Molecular Biology Source Type: research
Knockdown of SOX9 alleviates tracheal fibrosis through the Wnt/ β-catenin signaling pathway
AbstractTrachealfibrosis is an important cause of tracheal stenosis without effective treatments, and new drug targets need to be developed. The role of SOX9 in the injury and repair of the trachea is unknown; this study aims to investigate the role of SOX9 in the regulation of tracheal fibrosis based on clinical samples from patients with tracheal injury and a model of tracheal fibrosis produced by tracheal brushing in rats. The results showed that the expressions of SOX9 and mesenchymal and ECM-related indicators were increased in the injury and fibrosis of the trachea in patients and rats. Serum SOX9 levels exhibited a ...
Source: Journal of Molecular Medicine - October 3, 2022 Category: Molecular Biology Source Type: research
Growth hormone/IGF-I-dependent signaling restores decreased expression of the myokine SPARC in aged skeletal muscle
AbstractSkeletal muscle exerts many beneficial effects on the human body including the contraction-dependent secretion of peptides termed myokines. We have recently connected the myokine secreted protein acidic and rich in cysteine (SPARC) to the formation of intramuscular adipose tissue (IMAT) in skeletal muscle from aged mice and humans. Here, we searched for inducers of SPARC in order to uncover novel treatment approaches for IMAT. Endurance exercise in mice as well as forskolin treatment in vitro only modestly activated SPARC levels. However, through pharmacological treatments in vitro, we identified IGF-I as a potent ...
Source: Journal of Molecular Medicine - September 30, 2022 Category: Molecular Biology Source Type: research
A novel ceRNA regulatory network involving the long noncoding NEAT1, miRNA-466f-3p and its mRNA target in osteoblast autophagy and osteoporosis
AbstractOsteoporosis (OP) is a systemic metabolic disorder characterized by a reduction in bone tissue volume. LncRNAs have been reported to act as regulators of several human diseases. Specifically, lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is involved in proliferation, differentiation and apoptosis in osteoclasts and bone marrow mesenchymal stem cells and regulates the occurrence and development of OP. However, the relationship between NEAT1 and osteoblast autophagy and its mechanism are still unclear. Western blotting of LC3 and P62 was used to evaluate the effect of fluid shear stress (FSS) on autophagy ...
Source: Journal of Molecular Medicine - September 28, 2022 Category: Molecular Biology Source Type: research
Underlying mechanisms of epithelial splicing regulatory proteins in cancer progression
AbstractCancer is the second-leading disease-related cause of global mortality after cardiovascular disease. Despite significant advances in cancer therapeutic strategies, cancer remains one of the major obstacles to human life extension. Cancer pathogenesis is extremely complicated and not fully understood. Epithelial splicing regulatory proteins (ESRPs), including ESRP1 and ESRP2, belong to the heterogeneous nuclear ribonucleoprotein family of RNA-binding proteins and are crucial regulators of the alternative splicing of messenger RNAs (mRNAs). The expression and activity of ESRPs are modulated by various mechanisms, inc...
Source: Journal of Molecular Medicine - September 27, 2022 Category: Molecular Biology Source Type: research
SUMOylation targeting mitophagy in cardiovascular diseases
AbstractSmall ubiquitin-like modifier (SUMO) plays a key regulatory role in cardiovascular diseases, such as cardiac hypertrophy, hypertension, atherosclerosis, and cardiac ischemia –reperfusion injury. As a multifunctional posttranslational modification molecule in eukaryotic cells, SUMOylation is essentially associated with the regulation of mitochondrial dynamics, especially mitophagy, which is involved in the progression and development of cardiovascular diseases. SUMOyla tion targeting mitochondrial-associated proteins is admittedly considered to regulate mitophagy activation and mitochondrial functions and dynamics...
Source: Journal of Molecular Medicine - September 26, 2022 Category: Molecular Biology Source Type: research
The serotonin receptor 3E variant is a risk factor for female IBS-D
In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reducedHTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance ofHTR3E in the pathogenesis of IBS-D. (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - September 19, 2022 Category: Molecular Biology Source Type: research
Acyloxyacyl hydrolase deficiency induces chronic inflammation and bone loss in male mice
In conclusion, the chronic inflammatory state of adult Aoah−/− mice promotes bone resorption. AOAH participates in bone metabolism, which is mainly mediated by inhibiting osteoclast differentiation. LPS may be a key mediator of the gut-bone axis, and targeting AOAH may represent a feasible strategy for the treatment of chronic inflammatory bone resorption.Key messagesAOAH knockout mice exhibited chronic inflammation mediated by LPS, and LPS may also serve as an important mediator in the regulation of bone metabolism in the gut-bone axis.AOAH regulated bone resorption by blocking the osteoclast differentiation via class...
Source: Journal of Molecular Medicine - September 16, 2022 Category: Molecular Biology Source Type: research
Transcription factor EB inhibits non-alcoholic fatty liver disease through fibroblast growth factor 21
This study may lay a basis for identifying new drug targets for NAFLD treatment.Key messagesTranscription factor EB (TFEB) is involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), and fibroblast growth factor 21 (FGF21) exerts a significantly positive effect on NAFLD.In the current study, we found that starvation led to an increase in liver lipids, which was reversed by re-feeding. Phosphorylated mTOR, ribosomal S6 kinase, TFEB, and FGF21 are involved in the above process. The increased expression of TFEB in NAFLD mice by tail vein injection of Ad-TFEB could reverse lipid deposition and metabolic chang...
Source: Journal of Molecular Medicine - September 14, 2022 Category: Molecular Biology Source Type: research
Elucidation of endothelial progenitor cell dysfunction in diabetes by RNA sequencing and constructing lncRNA –miRNA–mRNA competing endogenous RNA network
AbstractWith the rapid increase in the incidence of diabetes, non-healing diabetic wounds have posed a huge challenge to public health. Endothelial progenitor cell (EPC) has been widely reported to promote wound repairing, while its number and function were suppressed in diabetes. However, the specific mechanisms and competing endogenous RNA (ceRNA) network of EPCs in diabetes remain largely unknown. Thus, the transcriptome analyses were carried in the present study to clarify the mechanism underlying EPCs dysfunction in diabetes. EPCs were successfully isolated from rats. Compared to the control, diabetic rat-derived EPCs...
Source: Journal of Molecular Medicine - September 12, 2022 Category: Molecular Biology Source Type: research
Phase separation in immune regulation and immune-related diseases
AbstractPhase separation is an emerging paradigm for understanding the biochemical interactions between proteins, DNA, and RNA. Research over the past decade has provided mounting evidence that phase separation modulates a great variety of cellular activities. Particularly, phase separation is directly relevant to immune signaling, immune cells, and immune-related diseases like cancer, neurodegenerative diseases, and even SARS-CoV-2. In this review, we summarized current knowledge of phase separation in immunology and emerging findings related to immune responses as they enable possible treatment approaches. (Source: Journ...
Source: Journal of Molecular Medicine - September 9, 2022 Category: Molecular Biology Source Type: research
The multiple functions of PrPC in physiological, cancer, and neurodegenerative contexts
AbstractCellular prion protein (PrPC) is a highly conserved glycoprotein, present both anchored in the cell membrane and soluble in the extracellular medium. It has a diversity of ligands and is variably expressed in numerous tissues and cell subtypes, most notably in the central nervous system (CNS). Its importance has been brought to light over the years both under physiological conditions, such as embryogenesis and immune system homeostasis, and in pathologies, such as cancer and neurodegenerative diseases. During development, PrPC plays an important role in CNS, participating in axonal growth and guidance and different...
Source: Journal of Molecular Medicine - September 3, 2022 Category: Molecular Biology Source Type: research
Polypeptide N-acetylgalactosamine transferase 3: a post-translational writer on human health
AbstractPolypeptideN-acetylgalactosamine transferase 3 (ppGalNAc-T3) is an enzyme involved in the initiation of O-GalNAc glycan biosynthesis. Acting as a writer of frequent post-translational modification (PTM) on human proteins, ppGalNAc-T3 has key functions in the homeostasis of human cells and tissues. We review the relevant roles of this molecule in the biosynthesis of O-GalNAc glycans, as well as in biological functions related to human physiological and pathological conditions. With main emphasis in ppGalNAc-T3, we draw attention to the different ways involved in the modulation of ppGalNAc-Ts enzymatic activity. In a...
Source: Journal of Molecular Medicine - September 2, 2022 Category: Molecular Biology Source Type: research
Stress induces major depressive disorder by a neutral sphingomyelinase 2-mediated accumulation of ceramide-enriched exosomes in the blood plasma
AbstractMajor depressive disorder (MDD) is a very common, severe disease with a lifetime prevalence of ~ 10%. The pathogenesis of MDD is unknown and, unfortunately, therapy is often insufficient. We have previously reported that ceramide levels are increased in the blood plasma of patients with MDD and in mice with experimental MDD. Here, we demonstrate that ceramide-enriched exosomes in the blo od plasma are increased in mice with stress-induced MDD. Genetic studies reveal that neutral sphingomyelinase 2 is required for the formation of ceramide-enriched exosomes in the blood plasma. Accordingly, induced deficiency o...
Source: Journal of Molecular Medicine - August 31, 2022 Category: Molecular Biology Source Type: research
