Ask about this productRelated genes to: ROCK1 antibody
- Gene:
- ROCK1 NIH gene
- Name:
- Rho associated coiled-coil containing protein kinase 1
- Previous symbol:
- -
- Synonyms:
- p160ROCK
- Chromosome:
- 18q11.1
- Locus Type:
- gene with protein product
- Date approved:
- 1997-10-10
- Date modifiied:
- 2016-10-05
Related products to: ROCK1 antibody
Related articles to: ROCK1 antibody
- To investigate the effects of the sphingosine-1-phosphate receptor-2 (S1PR2) inhibitor JTE-013 on pulmonary fibrosis in silicosis mice and its underlying molecular mechanisms. In October 2024, 40 SPF male C57BL/6J mice were randomly divided into control group, JTE-013 control group, silicosis model group, and JTE-013 treatment group. A silicosis model was established by non-exposure intratracheal instillation of SiO(2) suspension. One week after model was establishment, mice in the JTE-013 treatment group were intraperitoneally injected with JTE-013 (10 mg/kg, twice a week for a total of 6 times), while mice in other groups were intraperitoneally injected with the same volume of normal saline. After 28 d of modeling, the lung coefficients of mice in each group were detected. The lung tissues were stained with HE, Masson, and Sirius Red to assess pathological damage and collagen deposition. The content of hydroxyproline (HYP) was determined. The expressions of S1PR2, epithelial-mesenchymal transition (EMT) marker proteins [E-cadherin (E-cad), Vimentin, α-smooth muscle actin (α-SMA) ], and Ras homolog family member A/Rho-related coiled helix kinase 1 (RhoA/ROCK1) pathway proteins were detected by protein immunoblotting method. Human alveolar epithelial A549 cells were cultured in vitro. The cells were divided into normal control group (cultured in complete medium for 26 h), JTE-013 control group (cultured in medium prepared to 1 μmol/L JTE-013 solution for 26 h), SiO(2) treatment group (cultured for 2 h with normal medium, then treated with 50 μg/ml SiO(2) suspension for 24 h), and SiO(2)+JTE-013 treatment group (pre-treated with 1 μmol/L JTE-013 for 2 h, then added 50 μg/ml SiO(2) suspension for 24 h). After group intervention, the expression levels of S1PR2, EMT-related proteins, RhoA and ROCK1 in the cells were detected. For the normally distributed measurement data, one-way ANOVA analysis of variance was used for inter-group comparison, and LSD- test was used for pairwise comparison. Compared with the control group, the mice in the silicosis model group had a significant decrease in body weight, and their lung coefficient and HYP content were significantly increased (<0.05), silicotic nodules formed in the lungs, accompanied by collagen deposition. And the expression levels of SIPR2 protein, EMT-related proteins Vimentin, α-SMA, and the RhoA and ROCK1 proteins in signaling pathway were significantly increased, while the expression level of the epithelial marker E-cad was significantly decreased (<0.05). Compared with the silicosis model group, the mice in the JTE-013 treatment group had a significantly increase in body weight, the lung coefficient and HYP content were significantly decreased (<0.05), the pulmonary fibrosis was significantly reduced. And the expression levels of SIPR2 protein, EMT-related proteins Vimentin, α-SMA, and the RhoA and ROCK1 proteins in the signaling pathway were significantly decreased, while the expression level of the epithelial marker E-cad was significantly increased (<0.05). In the in vitro experiments, compared with the normal control group, the expression levels of EMT-related proteins Vimentin, α-SMA and the proteins RhoA and ROCK1 in the signaling pathway in the SiO(2) treatment group were significantly increased, while the expression level of the epithelial marker E-cad was significantly decreased (<0.05). Compared with the SiO(2) group, the expression levels of EMT-related proteins Vimentin, α-SMA, and the proteins RhoA and ROCK1 in the signaling pathway in the SiO(2)+JTE-013 treatment group were significantly decreased, while the expression level of the epithelial marker E-cad was significantly increased (<0.05) . JTE-013 can alleviate the pulmonary fibrosis in silicosis mice, which may be related to the inhibition of the EMT process through the RhoA/ROCK1 signaling pathway. - Source: PubMed
Zhang JWu SChen Y HZou MLi Y - Rho-associated coiled-coil kinase 1 (ROCK1) and Transforming Growth Factor Beta Receptor 1 (TGFBR1) are pivotal mediators of epithelial-mesenchymal transition (EMT), cytoskeleton remodeling, cell adhesion, and cancer metastasis. Their simultaneous inhibition offers a promising therapeutic strategy to disrupt cancer metastasis. This study integrates machine learning (ML)-based predictive QSAR (Quantitative Structure Activity Relationship) modeling, structure-activity relationship (SAR) analysis, ML-based virtual screening to identify dual inhibitors targeting both ROCK1 and TGFBR1. Bioactivity data with SMILES representation of ROCK1 and TGFBR1 inhibitors were sourced from ChEMBL. Molecular descriptors and fingerprints (e.g., Morgan, AtomPairs2D, etc) were computed using RDKit and PaDEL to encode molecular properties. Analysis of chemical similarity using Tanimoto coefficients identified activity-cliff pairs of compounds with high structural similarity but significant activity differences. QSAR models were developed using individual and combined fingerprints, with additional strategies such as excluding activity cliff pairs and stratified sampling based on pIC quantiles. Predictive machine learning models, including Random Forest (RF), Gradient Boosting (GB), XGBoost (XGB), K-Nearest Neighbors (KNN), Support Vector Machines (SVM), and Ridge Regression (RR), demonstrated robust performance (R > 0.6). The best ROCK1 and TGFBR1 models (RF Regressor) were used to screen a library of 1,48,684 compounds, resulting in the identification of a Hit (2-(1H-1,3-benzodiazol-1-yl)-N-[3-(1H-pyrazol-4-yl)phenyl]propanamide) with predicted dual ROCK1 (pIC = 7.29) and TGFBR1 (pIC = 7.00) inhibitory activity. Further, docking and molecular dynamics simulations of the Hit showed strong and stable interaction with both the targets hinge region residues, suggesting potential dual target inhibition activity. - Source: PubMed
Publication date: 2026/04/28
Kalita BikashitaCoumar Mohane Selvaraj - Neutrophil migration to bacterial infection sites is key for host defense. Host ribosomal protein SA (RPSA) has been recently reported to regulate the anti-infection immunity of immune cells; however, its role in neutrophil migration remains unclear. Here, using myeloid-specific Rpsa-deficient mice, we found that RPSA deletion inhibited neutrophil infiltration and markedly exacerbated Streptococcus suis serotype 2 infection. Adoptive cell transfer and neutrophil depletion assays identified RPSA as vital for the anti-infective function of neutrophils. Mechanistically, RPSA deficiency induced the overexpression of olfactomedin 4 (OLFM4), which in turn inhibited the activation of the RhoA/ROCK1/pMLC2 signaling pathway, reduced MYH9 expression, and caused aberrant MYH9 translocation from the uropod to the cytosol in migrating neutrophils. Ultimately, this disrupted cytoskeletal polarization and uropod extension, thereby abrogating migratory function. Clinically, septic patients' neutrophils exhibited reduced RPSA and elevated OLFM4 expression, a phenotype that correlated with a marked impairment of migratory capacity. Therapeutic targeting of the RPSA-OLFM4 axis restored neutrophil migration and improved disease outcomes in both S. suis 2-infected and septic mice. Thus, our findings demonstrate that RPSA promotes neutrophil migration via downregulating OLFM4 to counter bacterial infection, and establish the RPSA-OLFM4 axis as a critical immune migratory checkpoint in host antibacterial immunity. - Source: PubMed
Publication date: 2026/04/25
Wu TongYang XiangruiLei SiyuWei ShaopengWang WeiSun YiJiang HexiangJia XiuwenTian YanyanZhang KaixinZhang YufanChen HaizhenHuang JingLi FengyangLi NaLei Liancheng - - Source: PubMed
Publication date: 2026/04/24
Cindra Sant'Ana MarllonMaschietto MarianaPaz Leal Danielade Santos de Oliveira RicardoFerreira Euzébio MayaraDos Santos Antonio CarlosNeder LucianoScrideli Carlos AlbertoTerci Valera Elvis - Glioblastoma (GBM) exhibits profound therapy resistance and inevitable recurrence, driven predominantly by glioblastoma stem cells (GSCs). S100A8 is positively associated with glioblastoma malignancy, but its expression and molecular mechanism in GSCs are poorly understood. Here, we demonstrated that S100A8 was highly expressed in GSCs and closely associated with shorter overall survival in GBM patients. The results showed that S100A8 maintained GSCs stemness by promoting cholesterol synthesis. Mechanistically, S100A8 bound to plasma membrane-localized RAGE, triggering ROS generation. Elevated ROS oxidized intracellular S100A8 at the Cys42 residue, thereby enhancing its affinity for mTORC1, subsequently inducing SREBP2-driven cholesterol synthesis. Furthermore, ROCK1-mediated phosphorylation of S100A8 at Thr3/Ser90, which stabilized S100A8 by impairing its binding to Fbxo10 and inhibiting the subsequent ubiquitination-mediated degradation. Our study reveals the S100A8-ROS-mTORC1 axis as a cholesterol metabolic vulnerability in GSCs, providing new insights into cholesterol metabolism and highlighting novel metabolism therapeutic strategies in GBM. - Source: PubMed
Publication date: 2026/04/20
Cai WanzhiHu JingmingChen ChengzhiShi HaoXu LeiZhu ShenghaoLiu NingWang XiuxingRich Jeremy NTu YimingJi Jing