Smad3 (Phospho_Ser425) Antibody
- Known as:
- Smad3 (Phospho_Ser425) Antibody
- Catalog number:
- E011325-1
- Product Quantity:
- 50ug
- Category:
- Antibodies
- Supplier:
- EnoGene
- Gene target:
- Smad3 (Phospho_Ser425) Antibody
Related genes to: Smad3 (Phospho_Ser425) Antibody
- Gene:
- SMAD3 NIH gene
- Name:
- SMAD family member 3
- Previous symbol:
- MADH3
- Synonyms:
- JV15-2, HsT17436
- Chromosome:
- 15q22.33
- Locus Type:
- gene with protein product
- Date approved:
- 1996-11-15
- Date modifiied:
- 2016-10-05
Related products to: Smad3 (Phospho_Ser425) Antibody
Related articles to: Smad3 (Phospho_Ser425) Antibody
- Chronic kidney disease (CKD) remains a major global health burden, and renal fibrosis is a key pathological driver of CKD progression. Homeodomain-interacting protein kinase 2 (HIPK2) has emerged as a potential therapeutic target because of its involvement in TGF-β/Smad3-mediated fibrotic signaling and NF-κB-driven inflammatory responses. In this study, a series of 2, 4-disubstituted pyrimidine derivatives were designed and synthesized as HIPK2 inhibitors. Among them, A6 (AF-1) and B11 (AF-2) exhibited potent HIPK2 inhibitory activity, with IC values of 0.36 and 0.56 μM, respectively, together with improved subtype selectivity over HIPK1 and HIPK3. Cellular thermal shift assays showed that AF-1 and AF-2 increased the thermal stability of endogenous HIPK2 in both NRK-49F and HK-2 cells, supporting intracellular target engagement. In TGF-β1-stimulated NRK-49F cells and HK-2 cells, both compounds reduced the expression of fibrosis-related markers, including fibronectin, collagen I, and α-SMA. AF-1 and AF-2 also inhibited the proliferation and migration of NRK-49F cells and attenuated TNF-α-induced NF-κB activation in HK-2 cells. In a 0.2% adenine-diet-induced mouse model of CKD, AF-1 and AF-2 alleviated renal tubular injury and collagen deposition, demonstrating significant renoprotective and antifibrotic effects in vivo. Collectively, AF-1 and AF-2 represent antifibrotic candidates with a new chemical scaffold, submicromolar HIPK2 inhibitory activity, and improved subtype selectivity within the HIPK family. Although further optimization is required to improve their pharmacokinetic and drug-like properties, these findings provide a new structural basis for the development of HIPK2 inhibitors with enhanced HIPK family selectivity for the treatment of CKD-associated renal fibrosis. - Source: PubMed
Publication date: 2026/08/10
Hu XinlanOuyang HanyiFeng ChunyuWu YanYao MengmengXu JieChen ZhuoLi Qianbin - Chronic lung diseases, including asthma, chronic obstructive pulmonary disease, bronchiectasis, and idiopathic pulmonary fibrosis, are clinically distinct but share epithelial injury, host-defense, inflammatory, and remodeling processes. We integrated European-ancestry genome-wide association study (GWAS) summary statistics for these four diseases using genomic structural equation modeling to construct a multivariate chronic lung disease (mvCLD) factor. Variant-level association testing was combined with genomic control assessment, locus annotation, GWAS-by-subtraction, fine-mapping, transcriptomic prioritization, pathway enrichment, single-cell spatial mapping, and heritability partitioning. For discovery, across 6,255,777 autosomal variants, mvCLD identified 2067 genome-wide significant variants, 30 loci, and 53 lead variants. Five lead variants were genome-wide significant for mvCLD but not for any component disease and showed high-confidence fine-mapping support. For gene prioritization, transcriptomic and gene-level analyses prioritized 21 candidate genes, including , , , , , , and . In exploratory functional analyses, enrichment analyses converged on interleukin, cytokine-receptor, JAK-STAT, interleukin-4/interleukin-13, thymic stromal lymphopoietin, asthma, and lung fibrosis pathways. Exploratory single-cell spatial mapping, based on a mouse embryonic atlas, showed the strongest overall enrichment in the lung annotation, although cross-dataset cell-type and tissue analyses did not reach significance after false discovery rate correction; heritability partitioning implicated conserved and active regulatory elements. These findings support a shared epithelial-immune and cytokine-regulatory genetic architecture across major chronic lung diseases and nominate biologically coherent candidate genes and pathways for future functional and translational studies. - Source: PubMed
Publication date: 2026/08/02
Liao Chung-ChihLiao Ke-RuLi Jung-Miao - Thoracic aortic dissection (TAD) associates with a high mortality rate. Treatment options are limited and mainly consist of surgical repair at critical aortic diameters as current pharmacological interventions are unable to stop disease progression. Despite the existence of different mouse models for thoracic aortic aneurysm (TAA) and TAD, the underlying disease mechanisms remain elusive. In humans, loss-of-function of SMAD3 or SMAD6 increases the risk for TAA. We therefore targeted both ohnologs of smad3 and smad6 in zebrafish in order to further investigate their contribution to aortic homeostasis. We found an increased diameter of the ventral aorta in smad3a;smad3b double knockout (smad3a/b DKO) zebrafish larvae, while smad6a;smad6b (smad6a/b DKO) zebrafish larvae have a reduced aortic diameter. Smad3a/b DKO survive normally to adulthood, but smad6a/b DKO die before the age of 8 months due to dissections and ruptures in the ventral aorta. Smad6a/b DKO zebrafish also show hypoplasia of the aortic arches and the distal part of the ventral aorta. Surprisingly, the smad3a;smad3b;smad6a;smad6b quadruple knockout (qKO) zebrafish model has normal survival and a milder vascular phenotype compared to the smad6a/b DKO. RNA sequencing of zebrafish larvae indicates upregulation of pathways related to melanogenesis, ribosome, blood vessel development and carboxylic acid transport, and downregulation of negative regulation of endopeptidase activity and immune system. Transcriptomic data of damaged aorta compared with healthy control aorta identifies significant differences in oxidative phosphorylation, mitochondrial function, extracellular matrix and the citrate cycle. In conclusion, data from our novel zebrafish models of thoracic aortic dissection and rupture indicate that SMAD3 function has an important modifying effect on the severe aortic manifestations induced by loss of SMAD6. - Source: PubMed
Publication date: 2026/08/12
Vanhooydonck MichielVerlee MaximSilva Marta SantanaPottie LoreBoel AnnekatrienVan Impe MatthiasDe Saffel HannaCaboor LisaBonnin AnneSegers PatrickDe Clercq AdelbertGansemans YannickVan Nieuwerburgh FilipSyx DelfienWillaert AndySips PatrickCallewaert Bert - The ADAP (adhesion and degranulation-promoting adapter protein)-SKAP1 signaling module is essential for TCR-mediated activation and LFA-1-dependent adhesion; however, its role in coordinating CD8 T cell differentiation remains unclear. Here, we show that ADAP acts as a negative regulator of CD8 T cell response. During acute LCMV-Armstrong infection, ADAP deficiency enhances CD8 T cell effector expansion and function, as evidenced by increased IFN-γ and granzyme B expression, and subsequently favors the formation of central memory-like CD8 T cells (CD44 CD62L). RNA sequencing (RNA-seq) analysis identified ZEB2 as one of the most significantly upregulated transcription factors in CD8 T cells. Mechanistically, ADAP interacts with the E3 ubiquitin ligase TRIM21 to facilitate K48-linked polyubiquitination and degradation of ZEB2. This, in turn, reduces the binding of ZEB2 to the promoter. Collectively, our study identifies a previously uncharacterized ADAP-TRIM21-ZEB2 axis that regulates CD8 T cell differentiation, providing new mechanistic insights into the control of T cell fate decisions. - Source: PubMed
Publication date: 2026/08/01
Lu JiajiaYang FanLi YanliZhang PengchaoJia TengfeiLiu Hebin - Preeclampsia (PE) is a severe pregnancy-specific disorder featured by insufficient extravillous trophoblast (EVT) invasion and impaired spiral artery remodeling. Pregnancy-specific beta-1-glycoprotein 2 (PSG2), a placenta-derived protein, is significantly elevated in the serum of PE patients, yet its exact role and underlying mechanism in trophoblast function remain largely unknown. We demonstrated that PSG2 was remarkably upregulated in PE placentas and its expression correlated positively with blood pressure and proteinuria, and negatively with gestational age and birth weight. In HTR-8/SVneo trophoblast cells, PSG2 overexpression suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), downregulated MMP2 and MMP9 expression, and induced S-phase cell cycle arrest and late apoptosis. Conversely, PSG2 knockdown exerted opposing effects without influencing cell cycle distribution or apoptosis. Immunofluorescence staining verified the co-localization of PSG2 and TGF-β1 in trophoblasts and placental tissues. Mechanistically, PSG2 activated the TGF-β/Smad3 signaling pathway, and the TGFBR1 inhibitor SB431542 effectively reversed PSG2-mediated inhibition of EMT, MMP2/MMP9 expression, and trophoblast functional impairment. In conclusion, highly expressed PSG2 in PE placentas contributes to PE pathogenesis by activating the TGF-β/Smad3 pathway, thereby inhibiting EMT and MMPs expression and attenuating trophoblast proliferation, migration, and invasion. These findings provide a novel molecular basis for understanding PE pathogenesis. - Source: PubMed
Publication date: 2026/08/10
Qin YanpingMeng ShengpingChen SiyingLv ChunyanWang ChenguangSu JunyouLin ChuzhenXu YajuanLin MengruWang Sumei