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Eosinophils improve cardiac function after myocardial infarction.

Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases. Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region. Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes. Mechanistic studies reveal roles of eosinophil IL4 and cationic protein mEar1 in blo

Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression.

BACKGROUND AND OBJECTIVE: To investigate the role of cardiomyocyte-derived BDNF as an endogenous regulator to decrease cardiac fibrosis, its underlying mechanism and therapeutic potential. METHODS: Single-nuclei RNA sequencing (snRNA-seq), KEGG, Gene Ontology and cell‒cell interaction analyses were performed to identify changes in cardiac cells, cardiac functions and pathways due to the conditional knockout of cardiomyocyte-derived BDNF (cardiomyocyte-BDNF-KO). Protein C-terminal sequencing, qPCR, WB, CCK8 assays, flow cytometry, BDNF-AAV9 treatment and histological staining were performed to

Angiotensin-converting-enzyme inhibitor prevents skeletal muscle fibrosis in myocardial infarction mice.

BACKGROUND: Transforming growth factor beta (TGF-β)-Smad2/3 is the major signaling pathway of fibrosis, which is characterized by the excessive production and accumulation of extracellular matrix (ECM) components, including collagen. Although the ECM is an essential component of skeletal muscle, fibrosis may be harmful to muscle function. On the other hand, our previous studies have shown that levels of angiotensin II, which acts upstream of TGF-β-Smad2/3 signaling, is increased in mice with myocardial infarction (MI). In this study, we found higher skeletal muscle fibrosis in MI mice compared

P311 induces the transdifferentiation of epidermal stem cells to myofibroblast-like cells by stimulating transforming growth factor β1 expression.

BACKGROUND: Epithelial to mesenchymal transition, especially to myofibroblasts, plays an important role in wound healing, fibrosis, and carcinogenesis. Epidermal stem cells (EpSCs) are responsible for epidermal renewal and wound re-epithelialization. However, it remains unclear whether and how EpSCs transdifferentiate into myofibroblasts or myofibroblast-like cells (MFLCs). Here, we provide the first evidence showing that P311 induces EpSC to MFLC transdifferentiation (EpMyT) via TGFβ1/Smad signaling. METHODS: Wound healing and mesenchymal features were observed in the P311 KO and P311 WT mou

Distribution of Smad mRNA and proteins in the rat brain.

Smad proteins are known to transduce the action of TGF-β superfamily proteins including TGF-βs, activins, and bone morphogenetic proteins (BMPs). In this study, we examined the expression of Smad1, -2, -3, -4, -5, and -8 mRNA in the rat brain by means of RT-PCR and in situ hybridization (ISH). In addition, we examined the nuclear accumulation of Smad1, -2, -3, -5, and -8 proteins after intracerebroventricular injection of TGF-β1, activin A, or BMP6 with immunohistochemistry to investigate whether TGF-β, activin, and/or BMP activate Smads in the rat brain. RT-PCR analysis revealed that Smad1, -

Отмена сигнала TGF-β/Smad2 с помощью GW788388 усиливает расчистку DENV-2 в макрофаге.

Гнездовая лихорадка, вызванная вирусом денге (DENV-1, -2, -3 и -4), затрагивает миллионы людей в тропических и субтропических регионах мира. Тяжелая денге коррелирует с высокой виремией и цитокиновой бурей, такими, как высокие уровни преобразующего фактора роста β1 (TGF-β1) в сыворотке пациента. В данном случае, сигнализация TGF-β1 была исследована в контексте внутривитровирусной расчистки. Макрофаги были заражены DENV-2 при MOI 5 и обработаны рецептором TGF-β 1 и 2, GW788388. Выражения TGF-β1, трансдукции сигнала и вирусная нагрузка были оценены через 48 часов после инфекции DENV-2 с помощью

Совпадение в аннотации оригинала
Dengue fever, caused by the dengue virus (DENV-1, -2, -3, and -4), affects millions of people in the tropical and subtropical regions worldw … ally active form increased threefold during infection, which was followed by the phosphorylation of Smad2 protein. Phosphorylation of Smad2 was reduced by treatment with GW788388 and it was correlated with reduced cytokine production. Importantly, treatment led to a dose-dependent reduction in viral load, ranging from 6.6 × 105 RNA copies/ml in untreated cultur …

[Exploring mechanism of gypenosides in inhibiting anoikis resistance in breast cancer via TGF-β1/Foxp3/RORγt signaling axis].

This study investigated the effect of gypenosides(GPs) on anoikis resistance(AR) in human triple-negative breast cancer(TNBC) MDA-MB-231 cells and explored the underlying mechanism involving the transforming growth factor β1(TGF-β1)/forkhead box protein P3(Foxp3)/retinoic acid-related orphan receptor γt(RORγt) signaling axis. An anoikis model was established using poly-HEMA coated plates, and cells were divided into normal adherent, anoikis model, GPs(100 μg·mL~(-1)), TGF-β1 inhibitor(LY, 10 μmol·L~(-1)), and GPs + LY groups. Cell viability, apoptosis, invasion and migration were assessed by C

Activin A exacerbates neonatal necrotizing enterocolitis via ALK4-mediated apoptosis and barrier disruption.

BACKGROUND: Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder in neonates, yet the role of Activin A (ACV A) in NEC pathogenesis remains unclear. METHODS: NEC was induced in neonatal mice through hypoxia, hypothermia, LPS, and formula feeding. An in vitro intestinal epithelial injury model was established using LPS-stimulated IEC-6 cells. Recombinant Activin A (rActivin A) and neutralizing antibody (anti-Activin A) were used for intervention. Comprehensive evaluations were performed to assess intestinal injury, barrier function (ZO-1 / Occludin / Claudin-1), infl

N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds

Direct moxibustion exerts an analgesic effect on cervical spondylotic radiculopathy by increasing autophagy via the Act A/Smads signaling pathway.

BACKGROUND: Direct moxibustion (DM) is reported to be useful for cervical spondylotic radiculopathy (CSR), but the analgesic mechanism remains unknown. Autophagy plays a protective role in neuronal apoptosis, Act A/Smads signaling pathway has been confirmed to be associated with the activation of autophagy. The study aimed to explore the effect of DM on autophagy in rats with CSR and the involvement of Act A/Smads signaling pathway. METHODS: Rats were randomly divided into Sham, CSR, CSR + DM, CSR + DM + 3-MA (PI3K inhibitor), and CSR + DM + SB (Act A inhibitor) group. Three days after establ

MeCP2-421-mediated RPE epithelial-mesenchymal transition and its relevance to the pathogenesis of proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is a blinding eye disease. Epithelial-mesenchymal transition (EMT) of RPE cells plays an important role in the pathogenesis of PVR. In the current study, we sought to investigate the role of the methyl-CpG-binding protein 2 (MeCP2), especially P-MeCP2-421 in the pathogenesis of PVR. The expressions of P-MeCP2-421, P-MeCP2-80, PPAR-γ and the double labelling of P-MeCP2-421 with α-SMA, cytokeratin, TGF-β and PPAR-γ in human PVR membranes were analysed by immunohistochemistry. The effect of knocking down MeCP2 using siRNA on the expressions of α-SMA, phospho-

Apamin inhibits hepatic fibrosis through suppression of transforming growth factor β1-induced hepatocyte epithelial-mesenchymal transition.

Apamin is an integral part of bee venom, as a peptide component. It has long been known as a highly selective block Ca(2+)-activated K(+) (SK) channels. However, the cellular mechanism and anti-fibrotic effect of apamin in TGF-β1-induced hepatocytes have not been explored. In the present study, we investigated the anti-fibrosis or anti-EMT mechanism by examining the effect of apamin on TGF-β1-induced hepatocytes. AML12 cells were seeded at ∼60% confluence in complete growth medium. Twenty-four hours later, the cells were changed to serum free medium containing the indicated concentrations of a

Transforming growth factor beta-2 drives trabecular meshwork progenitor cell differentiation through SMAD2/3 signaling.

Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness, yet its underly mechanisms remain unclear. Elevated intraocular pressure (IOP), the only modifiable risk factor for POAG, arises from increased resistance to aqueous humor outflow within the conventional outflow pathway, which comprises the trabecular meshwork (TM) and the inner wall of Schlemm's canal. Dysfunction and cellular loss within this pathway, particularly in the TM, are consistent features of the disease; however, the mechanisms responsible for impaired tissue maintenance and regenerative failure remain u

Silica's silent threat: Contributing to skin fibrosis in systemic sclerosis by targeting the HDAC4/Smad2/3 pathway.

Nowadays, silica products are widely used in daily life, especially in skin applications, which inevitably increases the risk of silica exposure in general population. However, inadequate awareness of silica's potential hazards and lack of self-protection are of concern. Systemic sclerosis (SSc) is characterized by progressive tissue fibrosis under environmental and genetic interactions. Silica exposure is considered an important causative factor for SSc, but its pathogenesis remains unclear. Within this study, we showed that lower doses of silica significantly promoted the proliferation, migr

Experimental Study of YaJieShaBa Antialcoholic Hepatic Fibrosis Through TGF-β1/Smad Signaling Pathway.

OBJECTIVE: This study aimed to clarify the pharmacodynamic effects of YaJieShaBa (YJSB) against alcoholic hepatic fibrosis (HF) and elucidate its mechanism in regulating the transforming growth factor-β1 (TGF-β1)/Smad pathway. METHODS: Induce the alcoholic HF model in rats using 56% ethanol (10 mL/kg). The pharmacological efficacy of YJSB in combating liver fibrosis was evaluated through comprehensive assessments of key indicators: body weight, liver mass and index, biochemical liver function parameters (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), liver fibrosis biom

Investigating the regulation of the miR-199a-3p/TGF-β/Smad signaling pathway by BSHXF drug-containing serum combined with ADSCs for delaying intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IDD) significantly contributes to low back pain (LBP), yet effective treatment options are scarce. BSHXF, a classical traditional Chinese medicine formula, demonstrates dual pharmacological actions: tonifying kidneys, strengthening bones, activating blood circulation, and resolving stasis. It has been widely used in IDD management. Given its potential, combining BSHXF with miRNA regulation and stem cell therapy may enhance therapeutic outcomes by targeting molecular and cellular pathways underlying IDD pathogenesis. AIM OF THE STUDY: IDD is recogn

Systemic effect of FHL1 on neuromuscular junction and myotube formation via insulin-like growth factor and myostatin signaling pathways.

Four-and-a-half LIM domain protein 1 (FHL1) is a member of the FHL protein family that serves as a scaffold protein to maintain normal cellular structure and function. Its mutations have been implicated in multiple muscular diseases. These FHL1 related myopathies are characterized by symptoms such as progressive muscle loss, rigid or bent spine, even cardiac or respiratory failure in some patients, which implies pathological problems not only in muscles, but also in the nervous system. Moreover, decreased FHL1 protein level has been found in patients with FHL1 mutations, indicating the protein

Angiotensin II-driven TGF-β1 increases platelet PAR4 expression enhancing thrombotic risk in hypertension.

BACKGROUND AND AIMS: Hypertensive patients exhibit heightened susceptibility to pro-thrombotic state, elevating their cardiovascular event risk. G protein-coupled receptors (GPCRs) serve as central mediators of platelet function; however, the mechanisms through which GPCRs contribute to platelet hyperreactivity remain unclear. This study explores protease-activated receptor 4 (PAR4) on platelet hyperactivation in hypertension. METHODS: Platelet GPCR expression from 150 hypertensive patients, spontaneously hypertensive rats (SHRs), and L-NAME-induced hypertensive mice were analysed using RNA-s

ISG15 deficiency in hepatic stellate cells promotes TGFβ2-induced liver fibrosis by counteracting CREB1 ISGylation.

BACKGROUND: Interferon (IFN)-stimulated gene 15 (ISG15) is a downstream molecule of the IFN pathways central to many cellular processes. ISG15 mainly exerts its function through a post-translational modification process known as ISGylation. OBJECTIVE: In this study, the role of ISG15 in the activation of hepatic stellate cells (HSCs) and liver fibrosis was examined. DESIGN: Liver fibrosis was established by carbon tetrachloride (CCl4), bile duct ligation (BDL) surgery and metabolic dysfunction-associated steatohepatitis (MASH) diet between HSC-specific deletion of ISG15 (ISG15cKO) and wild t

Baicalein alleviates high glucose-induced mesangial cell fibrosis and inflammation in diabetic nephropathy: roles of AMPK activation and TGF-β1 inhibition.

BACKGROUND: Diabetic nephropathy (DN), a major diabetic microvascular complication, is the primary cause of end-stage renal disease worldwide. It is characterized by mesangial cell fibrosis and chronic inflammation, which current treatments cannot completely reverse. Baicalein, a major flavonoid from Scutellaria baicalensis Georgi, has anti-inflammatory and antifibrotic activities, but its role and mechanism in high glucose (HG)-induced mesangial cell injury (a key DN feature) remain unclear. OBJECTIVE: This study investigated baicalein's effects on rat glomerular mesangial cells (HBZY-1) and