Smad3 AND Beta cells

BACKGROUND: Extracellular vesicles (EVs) and their cargoes, including MicroRNAs (miRNAs) play a crucial role in cell-to-cell communication. We previously demonstrated the upregulation of bta-mir-148b in EVs from oviductal fluid of cyclic cows. This miRNA is linked to the TGF-β pathway in the cell proliferation. Our aim was to verify whether miR-148b is taken up by embryos through gymnosis, validate its target genes, and investigate the effect of miR-148b supplementation on early embryo development and quality...

BACKGROUND: Peritoneal fibrosis is the prevailing complication induced by prolonged exposure to high glucose in patients undergoing peritoneal dialysis. METHODS: To elucidate the molecular mechanisms underlying this process, we conducted an integrated analysis of the transcriptome and chromatin accessibility profiles of human peritoneal mesothelial cells (HMrSV5) during high-glucose treatment. RESULTS: Our study identified 2775 differentially expressed genes (DEGs) related to high glucose-triggered pathological changes, including 1164 upregulated and 1611 downregulated genes...

BACKGROUND: FOXL2 is a transcription factor expressed in ovarian granulosa cells. A somatic variant of FOXL2 (c.402 C > G, p.Cys134Trp) is the hallmark of adult-type granulosa cell tumours. METHODS: We generated KGN cell clones either heterozygous for this variant (MUT) or homozygous for the wild-type (WT) allele by CRISPR/Cas9 editing. They underwent RNA-Seq and bioinformatics analyses to uncover pathways impacted by deregulated genes. Cell morphology and migration were studied...

The spontaneous migration of bone marrow neutrophils (BMNs) is typically induced by distant tumor cells during the early stage of the tumor and critically controls tumor progression and metastases. Therefore, identifying the key molecule that prevents this process is extremely important for suppressing tumors. Interleukin-37 (IL-37) can suppress pro-inflammatory cytokine generation via an IL-1R8- or Smad3-mediated pathway. Here, we demonstrate that human neutrophil IL-37 is responsively reduced by tumor cells and the recombinant IL-37 isoform d (IL-37d) significantly inhibits spontaneous BMN migration and tumor lesion formation in the lung by negatively modulating CCAAT/enhancer binding protein beta (C/EBPβ) in a Lewis lung carcinoma (LLC)-inducing lung cancer mouse model...

Paeonol (2-hydroxy-4-methoxyphenylacetophenone) is a natural phenolic component isolated from the root bark of peony with multiple pharmacological activities and has been proven to have anti-cancer effects. The objective of this study is to investigate the influence mechanism of paeonol on the proliferatory and apoptotic activities of ovarian cancer (OC) cells by modulating the transforming growth factor beta (TGF-β)/Smad3 pathway. The SKOV3 cells were pretreated with various concentrations of paeonol (0, 25, 50, 100, 200, 400 μg/mL) for 48 hours to determine the optimal experimental concentration of paeonol...

BACKGROUND: Carcinoma of the breast, a prevailing factor in female mortality worldwide, involves dysregulation of lncRNAs and microRNAs. AIM: The main goal of this research was to predict and experimentally examine the LINC01405 expression status in breast cancer subtypes, along with investigation of its interaction with miR-29b and miR-497-5p that results in regulating PI3-Kinase, WNT, and TGF-beta signaling pathways. METHODS AND RESULTS: We performed a meta-analysis of five GEO datasets, encompassing microarray and RNA-seq data, to identify differentially expressed genes...

The secreted protein transforming growth factor-beta (TGFβ) plays essential roles, ranging from cell growth regulation and cell differentiation in both normal and cancer cells. In melanoma, TGFβ acts as a potent tumor suppressor in melanoma by blocking cell cycle progression and inducing apoptosis. In the present study, we found TGFβ to regulate cancer stemness in melanoma through the Smad signaling pathway. We discovered that TGFβ/Smad signaling inhibits melanosphere formation in multiple melanoma cell lines and reduces expression of the CD133+ cancer stem cell subpopulation in a Smad3-dependent manner...

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. Epithelial-mesenchymal transition (EMT) is an essential player in these alterations. Scutellarin is isolated from Erigeron breviscapus. Its vascular relaxative, myocardial protective, and anti-inflammatory effects have been well established. This study was designed to detect the biological roles of scutellarin in asthma and its related mechanisms. The asthma-like conditions were induced by ovalbumin challenges...

Hypertrophic scar (HS) formation is a cutaneous fibroproliferative disease that occurs after skin injuries and results in severe functional and esthetic disability. To date, few drugs have shown satisfactory outcomes for the treatment of HS formation. Transforming growth factor-beta (TGF-β)/Notch interaction via small mothers against decapentaplegic 3 (Smad3) could facilitate HS formation; therefore, targeting TGF-β/ Notch interaction via Smad3 is a potential therapeutic strategy to attenuate HS formation...

The transforming growth factor beta (TGFβ) and Hippo signaling pathways are evolutionarily conserved pathways that play a critical role in cardiac fibroblasts during embryonic development, tissue repair, and fibrosis. TGFβ signaling and Hippo signaling are also important for cardiac cushion remodeling and septation during embryonic development. Loss of TGFβ2 in mice causes cardiac cushion remodeling defects resulting in congenital heart disease. In this study, we used in vitro molecular and pharmacologic approaches in the cushion mesenchymal cell line (tsA58-AVM) and investigated if the Hippo pathway acts as a mediator of TGFβ2 signaling...

PURPOSE: The aim of the study was to verify hypotheses: Are transforming growth factors TGFβ1-3, their receptors TGFβI-III, and intracellular messenger proteins Smad1-7 involved in the pathogenesis of kidney cancer? What is the expression of genes of the TGFβ/Smads pathway in renal cell carcinoma (RCC) tissues, peritumoral tissues (TME; tumor microenvironment), and in normal kidney (NK) tissue?. METHODS: Twenty patients with RCC who underwent total nephrectomy were included into the molecular analysis...

Skin fibrosis, the most obvious clinical manifestation of systemic sclerosis (SSc), has a high unmet need for treatment. Xanthohumol (Xn) has been shown to have beneficial effects on fibrotic diseases, but its efficacy in SSc remains unreported. This study aims to elucidate the effects and mechanisms of Xn on collagen synthesis in SSc skin fibroblasts (SScF). We found increased collagen production in SScF cultured in vitro, accompanied by dysregulated levels of oxidative stress. Cell experiments showed that Xn inhibited cell proliferation and promoted apoptosis...

Renal fibrosis is a typical pathological change in chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) is the predominant stage. Activation of macroautophagy/autophagy plays a crucial role in the process of EMT. Lycopene (LYC) is a highly antioxidant carotenoid with pharmacological effects such as anti-inflammation, anti-apoptosis and mediation of autophagy. In this study, we demonstrated the specific mechanism of LYC in activating mitophagy and improving renal fibrosis. The enrichment analysis results of GO and KEGG showed that LYC had high enrichment values with autophagy...

BACKGROUND: Numerous studies have investigated the associations between maternal nutritional status and various diseases, with the underlying mechanism often attributed to epigenetic changes. However, limited research has been conducted on the relationship between maternal nutrition and benign prostatic hyperplasia (BPH). In this study, we aimed to explore the potential association between maternal nutrition and BPH using an animal experiment and evaluating the findings through fluorescent immunostaining and genetic analysis...

Introduction: There is a steady increase in colorectal cancer (CRC) incidences worldwide; at diagnosis, about 20 percent of cases show metastases. The transforming growth factor-beta (TGF-β) signaling pathway is one of the critical pathways that influence the expression of cadherins allowing the epithelial-to-mesenchymal transition (EMT), which is involved in the progression of the normal colorectal epithelium to adenoma and metastatic carcinoma. The current study aimed to investigate the impact of a novel coordination complex of platinum (salicylaldiminato) PT(II) complex with dimethyl propylene linkage (PT-complex) on TGF-β and EMT markers involved in the invasion and migration of the human HT-29 and SW620 CRC cell lines...

The transforming growth factor-beta (TGFβ) signaling pathway plays crucial roles in the establishment of an immunosuppressive tumor microenvironment, making anti-TGFβ agents a significant area of interest in cancer immunotherapy. However, the clinical translation of current anti-TGFβ agents that target upstream cytokines and receptors remains challenging. Therefore, the development of small-molecule inhibitors specifically targeting SMAD4, the downstream master regulator of the TGFβ pathway, would offer an alternative approach with significant therapeutic potential for anti-TGF-β signaling...

This study aimed to investigate the influence of recombinant human erythropoietin (rHuEPO) on pentylenetetrazol (PTZ)-induced neuronal apoptosis in epilepsy rats, and to explore the signaling pathways related to the action. Healthy Sprague-Dawley rats aged 8 weeks old were randomly divided into 5 groups, namely, control group, PTZ model group, PTZ + rHuEPO intervention group, PTZ + SB431542 + rHuEPO intervention group and PTZ + SB431542 (TGF-β/Smad inhibitor) intervention group. The expressions of apoptotic proteins [tumor necrosis factor receptor 1 (TNFR1) and caspase-3] and the transforming growth factor-beta (TGF-β)/Smad signaling pathway-related proteins [phosphorylated smad3 (p-smad3) and TGF-β1] in the brain tissues were determined via Western blotting (WB)...

This research aimed to the study influence of fasudil (FAS) on myocardial fibrosis in rats with diabetes mellitus (DM) via the transforming growth factor-beta 1 (TGF-β1)/ small mothers against decapentaplegic (Smad) signaling pathway. A total of 30 Sprague-Dawley rats were randomly divided into a blank control group (Control group, n=10), DM model group (DM group, n=10) and FAS treatment group (FAS group, n=10), and their blood and myocardial tissues were collected. Then blood glucose (GLU) content, hepatic and myocardial function indexes, ejection fraction (EF) and other cardiac function parameters were detected, and ELISA was employed to determine the content of serum IL-6, IL-1 and TNF-α...

Diabetic kidney disease (DKD) is one of the leading causes to develop end-stage kidney disease worldwide. Pericytes are implicated in the development of tissue fibrosis. However, the underlying mechanisms of pericytes in DKD remain largely unknown. We isolated and cultured primary pericytes and rat mesangial cells (HBZY-1). Western blot and qRT-PCR analysis were used to explore the role and regulatory mechanism of Integrin β8/transforming growth factor beta 1 (TGF-β1) pathway. We also constructed pericyte-specific Integrin β8 knock-in mice as the research objects to determine the role of Integrin β8 in vivo...

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that controls various cellular processes. Protein phosphatase 6 (PP6) is an evolutionarily conserved serine/threonine protein phosphatase with diverse functions in cell signaling. However, it has not been linked to TGF-β signaling. We found that TGF-β treatment increased PP6 protein levels via transcriptional and post-translational regulation. Loss of the Ppp6c gene suppressed TGF-β-induced canonical Smad3 phosphorylation and its transcriptional activity...