TGFBR1 _ ALK_5 _ SKR4 Protein
- Known as:
- TGFBR1 _ ALK_5 _ SKR4 Protein
- Catalog number:
- 10459-H03H
- Product Quantity:
- 20
- Category:
- -
- Supplier:
- Smart Serology
- Gene target:
- TGFBR1 _ ALK_5 SKR4 Protein
Related genes to: TGFBR1 _ ALK_5 _ SKR4 Protein
- Gene:
- TGFBR1 NIH gene
- Name:
- transforming growth factor beta receptor 1
- Previous symbol:
- MSSE, ESS1
- Synonyms:
- ALK-5, ACVRLK4, ALK5, TBRI, TBR-i
- Chromosome:
- 9q22.33
- Locus Type:
- gene with protein product
- Date approved:
- 1993-09-30
- Date modifiied:
- 2018-01-05
Related products to: TGFBR1 _ ALK_5 _ SKR4 Protein
Related articles to: TGFBR1 _ ALK_5 _ SKR4 Protein
- Molecular autopsy increasingly identifies rare variants in heritable aortopathy and Loeys-Dietz spectrum genes among sudden-death decedents, yet classification and causal attribution remain challenging when a syndromic diagnosis was never established during life. We reviewed eight unrelated Florida medical examiner decedents ascertained by sudden or unexpected death under medical examiner jurisdiction, including laboratory-reported heterozygous missense variants spanning the Loeys-Dietz syndrome (LDS)/familial thoracic aortic aneurysm and dissection (FTAAD) gene spectrum (, , , and ). None had a premortem clinical diagnosis of LDS; ascertainment was therefore a variant-positive molecular autopsy series, not clinically diagnosed LDS. This illustrative series of eight cases cannot estimate prevalence, diagnostic yield, penetrance, or incidental-finding frequency. Autopsy (±premortem) phenotype-variant concordance was graded as strong, limited, discordant, or not assessable without treating death as evidence of pathogenicity or equating laboratory detection with clinical LDS diagnosis. Grades were assigned by the authors using predefined rules, were not blinded to laboratory class, and were reconciled by consensus discussion; inter-rater reliability was not quantified. Population, computational, and ClinVar annotations, together with multi-axis molecular triangulation, were retained as supplementary context only. Laboratory classifications were pathogenic in one case ( p.Arg487Gln, Case 1), likely pathogenic in another ( p.Glu428Asp, Case 3), and variants of uncertain significance (VUS) in the remaining cases. Strong phenotype-variant concordance mapped to two aortic-catastrophe decedents (Cases 1 and 3), limited concordance to two cases (Cases 4 and 5), and discordant presentations to four (Cases 2, 6, 7, and 8), including pulmonary thromboembolism without aortopathy, infant sudden death with competing cardiomyopathy-gene context, and ethanol-related death with a normal aorta ( Case 8). In this illustrative variant-positive series, 2/8 cases had strong autopsy-led concordance, 2/8 limited, and 4/8 discordant. Autopsy-led concordance grading distinguished two LDS-spectrum variants with strong phenotype-variant concordance for fatal ascending aortic catastrophe from six variants with limited or discordant support. Rare variants in , , , or should not be conflated with an LDS diagnosis or with the cause of death without concordant autopsy evidence. - Source: PubMed
Publication date: 2026/08/29
Fernández-Cadena JuanNaylor Edwin WBhattacharjee Arindam - Myelodysplastic syndrome (MDS) is characterized by S100A9-mediated constitutive innate immune activation that leads to the inflammatory death of hematopoietic stem/progenitor cells (HSPCs). This suppressive microenvironment includes the secretion of TGFβ and is phenocopied by the S100A9-transgenic (Tg) mice. However, the role of the different ALK/TGFB receptors in hematopoiesis or in S100A9-mediated inflammation is not understood. Primary low-risk MDS bone marrow mononuclear cells (BM-MNCs) were analyzed in vitro for hematopoietic restoration by an ALK4/ALK5 inhibitor (Vactosertib), an ALK2 inhibitor (TP-0184/Itacnosertib) and an ALK5/TGFBR1-specific inhibitor (TP-6379). Specimens significantly responded to TP-6379 treatment restoring hematopoiesis, with a positive bias for specimens harboring spliceosomal mutations. We previously shown that S100A9 drives phenotypic pathology of MDS, and it has been known to induce and cooperate with TGFβ in this disease. Hence, we treated healthy BM-MNC with recombinant human (rh) S100A9 where TP-6379 rescued the S100A9-reduced hematopoiesis. The effect of TP-6379 was validated in vivo in S100A9-Tg mice. Similar results were obtained with K562 cells, with or without the knock-in (KI) mutation in SF3B1, with strong sensitivity to rhS100A9 that was overcome by TP-6379. Hence, directly targeting TGFBR1/ALK5 with TP-6379 restores healthy hematopoiesis in low-risk MDS preclinical models. - Source: PubMed
Publication date: 2026/09/16
Razabdouski TiffanyDalton RobertCalescibetta AlexandraChristiansen SeanWard GraceAugello Anthony CMoon JungwonYun SeongseokVincellette NicoleWright GabrielaGlode Annelise JChen Dung-TsaKroeger JodiFoulks Jason MWarner Steven LDuan BinLiu BoWright Kenneth LEksioglu Erika A - Chloroxylenol (PCMX), a widely used phenolic disinfectant, is an emerging aquatic pollutant whose immunotoxicity remains poorly understood. This study employed zebrafish models to evaluate PCMX toxicity across a concentration range (0.25-7.5 mg/L) spanning environmentally detectable levels to higher, toxicologically informative concentrations. Acute exposure caused dose-dependent developmental defects, oxidative stress, and apoptosis in both embryos and adults. Embryonic toxicological assessment revealed a 96-h LC of 3.98 mg/L for larvae, with significant hatching reduction at ≥2 mg/L and malformation elevation at ≥0.5 mg/L. PCMX disrupted innate immunity by depleting neutrophils while paradoxically expanding macrophages, RNA-seq revealed 353 dysregulated genes in adult kidney, with KEGG enrichment identifying the MAPK pathway as a central hub. Network toxicology and molecular docking predicted moderate binding of PCMX to MAPK nodes (TGFBR1, GRB2, AKT1; -6.66 to -4.5 kcal/mol), corroborated by qPCR validation of MAPK and hematopoietic regulators (optn, atf3, irak3, prkcba, tgfbr2a, spi1a, c1qb, fosab). We propose that PCMX-induced oxidative stress converges on MAPK disruption, driving immune dysregulation and biased hematopoiesis, though this causal model is inferred from correlative evidence and requires functional validation. Despite the concentration gap, these findings show that PCMX, even at sublethal doses, can disrupt conserved immune and hematopoietic pathways, raising concern for aquatic organisms. - Source: PubMed
Publication date: 2026/09/23
Wu GongqingZhong XiaoyinFeng XintongYi Yunhong - Neurological manifestations of systemic sclerosis (SSc), including autonomic dysfunction and peripheral neuropathy, are clinically recognized, but their relationship to SSc tissue injury remains poorly defined. We integrated public SSc blood, PBMC, skin and single-cell transcriptomes with an external human peripheral nerve lesion reference to test whether neuroimmune programs are embedded in immune-vascular-fibrotic remodeling. Across four SSc cohorts, pathway analyses identified recurrent interferon activation and skin-enriched fibrosis/TGF-beta, vascular endothelial, chemokine, complement/phagocytosis, neuroimmune-core and peripheral nerve injury signatures. Rank-AUC, ssGSEA and same-size random gene-set analyses supported these findings, and 22 of 70 curated cohort-signature tests remained significant after global Benjamini-Hochberg correction. A 17-gene exploratory score retained moderate discrimination in independent whole blood (AUC = 0.759), but nested cross-validation and stability analyses supported its use as a molecular summary, not a clinical classifier. In GSE250152, 3972 genes were differentially expressed in human peripheral nerve lesions, and lesion-signature projection showed FDR-significant shifts in SSc skin. Single-cell analysis of 146,426 cells localized vascular, fibrotic, interferon, chemokine and selected neuroimmune signals mainly to fibroblast, endothelial, pericyte, T-cell and myeloid-associated skin compartments. Cell-type-frequency adjustment preserved the direction of all 15 highlighted compartment-signature effects, with seven remaining significant after global correction. Ligand-receptor analyses prioritized IL1B-IL1R1, TNF-TNFRSF1A, VEGFA-KDR and TGFB1-TGFBR1 as speculative expression-potential routes rather than demonstrated communication events. These data support a bounded model linking SSc-related neural vulnerability to an immune-vascular-fibrotic neuroimmune niche. Prospective neurologically phenotyped cohorts are required for clinical validation. - Source: PubMed
Publication date: 2026/09/18
Lu YangHe YingtongYao JiayingHuang ShuxuanChen WeiweiZheng Lifen - Autoimmune uveitis (AU) is a vision-threatening intraocular inflammatory disease characterized by disruption of ocular immune privilege, blood-retinal barrier (BRB) dysfunction, and progressive immune-mediated retinal injury. Although corticosteroids and conventional immunosuppressive therapies remain clinically effective, their long-term use is limited by adverse effects, relapse, and incomplete disease control. Ferroptosis is an iron-dependent form of regulated cell death driven by phospholipid peroxidation. It may provide a mechanistic link between oxidative stress, retinal cell injury, and inflammatory amplification. The retina is potentially susceptible because of its high oxygen demand, redox-active iron, and enrichment in polyunsaturated fatty acids. Direct evidence in AU, however, remains limited. In experimental autoimmune uveitis (EAU), fine particulate matter with an aerodynamic diameter of 2.5 μm or less (PM) induced ferroptosis-related changes in CD4 T cells and enhanced T helper 17 (Th17) pathogenicity, whereas modulation of transforming growth factor-β receptor 1 (TGFBR1) altered the glutathione peroxidase 4 (GPX4)/cystine-glutamate antiporter (xCT) axis, lipid peroxidation, and inflammatory severity. Studies in retinal pigment epithelial cells, retinal vascular endothelial cells, and other retinal injury models provide supporting evidence but should not be interpreted as direct proof in AU. This Mini Review examines ferroptosis as a potential contributor to BRB dysfunction and retinal inflammation. It separates direct AU/EAU findings from extrapolated evidence and highlights priorities for preclinical validation. - Source: PubMed
Publication date: 2026/09/02
Wang JunLi HepingXiong HaohanHe JiaQue TingFang Xing