ACTN4
- Known as:
- ACTN4
- Catalog number:
- 001099A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ACTN4
Related genes to: ACTN4
- Gene:
- ACTN4 NIH gene
- Name:
- actinin alpha 4
- Previous symbol:
- FSGS1
- Synonyms:
- -
- Chromosome:
- 19q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1992-03-26
- Date modifiied:
- 2016-10-05
Related products to: ACTN4
Related articles to: ACTN4
- Diabetic cardiomyopathy (DCM) features progressive fibrotic remodeling, but the shared molecular circuitry connecting diabetes mellitus (DM) to cardiomyopathy (CM) remains unclear. We integrated three DM- and three CM-related Gene Expression Omnibus (GEO) datasets and corrected batch effects with sva, verified by violin plots, principal component analysis (PCA), and silhouette coefficients computed on all common genes (DM: 0.9489 to -0.1016; CM: 0.9693 to -0.045; PC1/PC2 inter-batch differences abolished after normalization). Differential expression analysis identified 2562 DM Differentially expressed genes (DEGs) and 1414 CM DEGs, and their intersection yielded 91 common DEGs (51 upregulated, 40 downregulated). Protein-protein interaction (PPI) analysis prioritized 25 hub genes, whose enrichment profiles implicated insulin resistance/insulin signaling and adrenergic signaling in cardiomyocytes. TRRUST-based inference further defined a regulatory network centered on seven key genes (, , , , , , and ). To nominate a candidate target of oxymatrine (OMT), we performed docking and molecular dynamics (MD) simulations for representative complexes; OMT showed the most stable interaction with LTBP1, maintaining a consistently short pocket distance (~0.2 nm), the highest contact frequency, and the lowest MM/PBSA binding free energy (-15.32 kcal/mol), with favorable contributions dominated by van der Waals and nonpolar solvation terms. In primary cardiac fibroblasts (CFs), high glucose (HG, 30 mM glucose) induced proliferative and profibrotic activation, whereas OMT (0.4-0.8 mM) reduced HG-driven proliferation without detectable toxicity below 1.2 mM, suppressed FN, collagen I/III, and α-SMA expression, and inhibited migration. OMT also normalized HG-induced cell-cycle skewing by restoring G0/G1-phase occupancy and reducing S-phase entry, with effects comparable to metformin. Finally, HG increased LTBP1 expression and upregulated SMAD3/SMAD4, while OMT attenuated LTBP1 induction and suppressed downstream TGF-β/SMAD activation. Together, these data integrate cross-dataset transcriptomics with mechanistic validation to position LTBP1 as a putative antifibrotic node targeted by OMT, supporting inhibition of the LTBP1/TGF-β/SMAD axis as a candidate strategy to counter DCM-associated fibrosis. - Source: PubMed
Publication date: 2026/04/13
Tian LianqingGan ShiquanDu YouqiLong ChaowenChang ChuruiShen Xiangchun - Focal segmental glomerulosclerosis (FSGS) is one of the major causes of nephrotic syndrome, which can progress to end-stage renal disease, leading to kidney transplantation. Following renal transplantation, recurrence of FSGS (rFSGS) occurs in 30%-40% of patients with a high risk of graft loss. rFSGS typically presents with nephrotic-range proteinuria within days after post-transplantation. This review summarizes pathophysiology, biomarkers, and therapeutic strategies for rFSGS. Monogenic causes of FSGS, such as those caused by APOL1 mutation, show variable recurrence, while NPHS2 and ACTN4 show low recurrence of FSGS. Evidence suggests that idiopathic or primary FSGS is strongly associated with rFSGS, owing to podocyte structural damage caused by circulating permeability factors or immune dysfunction. Recent advances have identified biomarkers such as anti-nephrin antibodies, anti-CD40 antibodies, soluble tumor necrosis factor receptor 2 (sTNFR2), and soluble urokinase-type plasminogen activator receptor (suPAR) that help in early detection of recurrent FSGS. Post-transplant monitoring includes measuring urine protein-to-creatinine ratio (UPCR) and 24-h urine protein excretion, and a kidney biopsy. Preventive strategies, although including plasmapheresis and rituximab, show limited benefit and are not recommended for routine prophylaxis. Treatment options include plasmapheresis, immunoadsorption, and immunosuppressive drugs such as cyclophosphamide, rituximab, or calcineurin inhibitors. Recurrent FSGS is a clinical challenge with its multifactorial pathogenesis. Incorporating strategies such as genetic testing, risk stratification, and early detection with the help of biomarkers and early treatment can induce remission and preserve graft survival. Despite these advances, large prospective studies are still required for standardizing prevention and management strategies for rFSGS. - Source: PubMed
Publication date: 2026/03/30
Oatley ZacharyJaber DannyRayarakula NikhilGuirguis ThomasKhawaja LaythBhindwallam SiddharthAguirre MarisolRestrepo Jaime ManuelRaina Rupesh - Myocardial infarction (MI) is a leading cause of mortality around the globe. Cardiac patches offer a promising tissue engineering approach to facilitate the natural regeneration of damaged cardiac tissue. In this research, electroactive cardiac patches composed of alginate-gelatin (Alg-Gel) were fabricated using a freeze-drying technique. The scaffolds were subsequently coated with varying concentrations of reduced graphene oxide (rGO) to improve cardiac performance. The samples were thoroughly characterized in terms of their physicochemical, morphological, and biological properties, including morphology, cell viability, and gene expression. Notably, an rGO concentration of 0.3% w/v significantly improved the viability of bone marrow-derived mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs), while upregulating the expression of Connexin 43 (Conx43), tryptophan transporter 2 (TrpT-2), and actinin 4 (Actn4), all of which are critical for cardiac cell function. To evaluate therapeutic efficacy in vivo, Alg-Gel-rGO scaffolds seeded with BMSCs were implanted into the infarcted area of a rat model of MI. Echocardiographic, histological, and immunohistochemical analyses demonstrated that the prepared patches improved cardiac function, reduced scar thickness, and promoted angiogenesis, thereby supporting cardiac tissue repair. These findings suggest that Alg-Gel-rGO scaffolds hold significant potential for regenerating damaged myocardial tissue and enhancing post-MI recovery, representing a viable strategy in cardiac tissue engineering. - Source: PubMed
Publication date: 2026/03/28
Behzadi ElhamBaheiraei NafisehNaderi NasimNemati Fahimeh - Catch bonds, noncovalent supramolecular interactions whose lifetimes are increased by force, are ubiquitous in mechanical signaling pathways. The structural mechanisms of catch-bonding proteins remain unclear, hampering efforts to decipher how they are dysregulated in disease and exploit them therapeutically. The crosslinker α-actinin-4 (ACTN4) forms catch bonds with actin filaments (F-actin) to support the function of kidney podocytes, and its force-insensitive K255E variant causes autosomal dominant focal segmental glomerulosclerosis (FSGS). Using cryo-electron microscopy (cryo-EM), we find that wild-type ACTN4 engages F-actin in two modes, which biochemical experiments and molecular dynamics simulations assign as strong- and weak-binding states, while K255E ACTN4 only populates the strong binding state. By implementing a cryo-EM platform for applying tension across crosslinker-F-actin interfaces using myosin motors, we find that force promotes a weak-to-strong binding transition for wild-type ACTN4, consistent with a two-state catch bond model. Beyond providing mechanistic insight into how the K255E mutation disrupts ACTN4 F-actin catch-bonding in FSGS, this approach enables structural dissection of force-sensitive actin-binding proteins. - Source: PubMed
Publication date: 2026/04/12
Chin Alfred CMukadum FatemahReynolds Matthew JHocky Glen MAlushin Gregory M - Skeletal muscle is a central regulator of metabolic health, serving as the primary site of postprandial glucose uptake and playing a critical role in whole-body insulin sensitivity. Despite its importance, the molecular mechanisms governing muscle differentiation (myogenesis) and their modulation by metabolic interventions remain poorly defined. This study identifies the clathrin adaptor protein Picalm (phosphatidylinositol-binding clathrin assembly protein) as a novel regulator of myogenesis and investigates its regulation in response to exercise training and intermittent fasting. - Source: PubMed
Publication date: 2026/03/13
Gaugel JasminHaacke NeeleKuropka BennoJähnert MarkusRominger JuliaJonas WenkeSpeckmann ThiloRausch NiclasKleinert MaximilianWeigert CoraGarcia-Carrizo FranciscoSchulz Tim JEbner MichaelFreund ChristianSchürmann AnnetteVogel Heike