Ask about this productRelated genes to: LIMK1 antibody
- Gene:
- LIMK1 NIH gene
- Name:
- LIM domain kinase 1
- Previous symbol:
- -
- Synonyms:
- LIMK
- Chromosome:
- 7q11.23
- Locus Type:
- gene with protein product
- Date approved:
- 1996-03-14
- Date modifiied:
- 2015-09-03
Related products to: LIMK1 antibody
Related articles to: LIMK1 antibody
- Inflammatory bowel disease (IBD) involves complex immunometabolic dysregulation. Mitochondria-associated endoplasmic reticulum membranes (MAMs) link metabolic adaptation and inflammatory signaling, but gene expression features associated with MAM-related transcriptomic states in IBD remain unclear. Public transcriptomic datasets were integrated with a curated MAM-related gene set and herbal target information. Differential expression analysis, weighted gene coexpression network analysis, and machine learning-assisted feature selection were used to identify candidate genes. A two-gene nomogram was constructed and evaluated in discovery and independent validation datasets. Functional enrichment, immune deconvolution, regulatory network prediction, molecular docking, 200-ns molecular dynamics simulations, and preliminary quantitative polymerase chain reaction validation were performed. and were identified as candidate transcriptomic signature genes associated with IBD status and MAM-related transcriptional states, showing discriminatory performance in independent datasets. Both genes were associated with cytokine-cytokine receptor interaction and drug metabolism-cytochrome P450 pathways and were linked to macrophage-related immune states. Structural analyses suggested stable predicted binding between and 1-(4-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol and structurally plausible interactions between and palmatine. Preliminary tissue-level validation supported the disease-associated expression pattern of , whereas showed a consistent but nonsignificant upward trend. and may represent candidate transcriptomic signatures associated with MAM-related regulatory states in IBD. These findings should be interpreted as hypothesis-generating associations rather than evidence of MAM localization, functional causality, or therapeutic efficacy. Further protein-level and functional validation is required. - Source: PubMed
Publication date: 2026/08/12
Tu HoushuChen MenglinZhu PanpanHe LingHong Jing - Based on a strategy integrating topological feature identification and path priority assessment, this study systematically explored the efficacy targets and differentiated mechanisms of Colquhounia Root Tablets(CRT) in the "homotherapy for heteropathy" of rheumatoid arthritis(RA) and diabetic kidney disease(DKD). Firstly, candidate targets of CRT and disease-specific genes were retrieved by integrating multi-source databases and transcriptomic data. Protein-protein interaction(PPI) networks were constructed to identify key targets shared by or specific to RA and DKD via topological feature identification. Subsequently, a path priority assessment was introduced to calculate the average shortest path(ASP) values from drug targets to various pathological segments, thereby quantifying intervention efficacy to lock onto "dominant pharmacodynamic links". The predicted key functional axes were validated through animal experiments. The results indicated that the core targets of CRT for both diseases involved shared pathways such as phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt), tumor necrosis factor(TNF), and glycolysis/gluconeogenesis. Notably, path priority assessment revealed distinct dominant intervention links: for RA, CRT preferentially targeted "fibroblast-like synoviocyte(FLS) activation and invasion"(ASP=2.361), which mapped to the TNF-p38 mitogen-activated protein kinase(p38)-LIM domain kinase 1(LIMK1)-Cofilin1 axis to regulate cytoskeleton remodeling; for DKD, the dominant link was "filtration barrier injury and interstitial fibrosis"(ASP=2.295), converging on the TNF-poly(ADP-ribose) polymerase 1(PARP1)-signal transducer and activator of transcription 1(STAT1)-matrix metallopeptidase 9(MMP9) axis to mediate cellular senescence and senescence-associated secretory phenotype(SASP) secretion. Animal experiments confirmed that CRT significantly alleviated RA synovial invasion and DKD renal fibrosis by inhibiting these two differentiated signaling axes, respectively. By employing topological feature identification and path priority assessment, this study elucidates the scientific connotation of "homotherapy for heteropathy" of RA and DKD with CRT through both shared network regulation and intervention in disease-specific differential signaling axes associated with pharmacodynamic links. - Source: PubMed
Cai Bing-BingMao XiaMa Zhao-ChenXu Ming-ZhuLin YaLin NaZhang Yan-Qiong - Neonatal bilirubin encephalopathy is primarily characterized by central auditory dysfunction and cognitive impairments. However, the precise molecular mechanisms underlying bilirubin-induced neurotoxicity remain poorly understood, hindering the development of effective therapeutic strategies. Using kinase activity prediction tools based on quantitative phosphoproteomics, we identified ROCK2 (Rho-associated protein kinase 2) as a critical kinase regulating the phosphorylation of proteins associated with bilirubin exposure. Molecular docking and MicroScale Thermophoresis assays revealed a strong binding affinity between bilirubin and ROCK2. Interestingly, bilirubin increased ROCK2 protein expression without affecting its mRNA levels, and cycloheximide chase assays revealed enhanced ROCK2 stability, implicating post-translational regulation. While bilirubin did not directly activate ROCK2 kinase activity in vitro, it elevated phosphorylation of its substrate LIMK1, suggesting that ROCK2 accumulation amplifies downstream signaling. In primary rat neurons, ROCK2 inhibitors (Belumosudil and Y-27632) ameliorated bilirubin-induced loss of mitochondrial membrane potential and neuronal cell death. Furthermore, using ROCK2 inhibitors and mice, we demonstrated that modulation of ROCK2 significantly alleviated bilirubin-induced auditory deficits and cognitive impairments. These behavioral improvements were linked to restored excitatory synaptic transmission in the cochlear nucleus and reduced dendritic damage in hippocampal neurons. These findings position ROCK2 as a promising molecular target for therapeutic intervention in bilirubin encephalopathy. - Source: PubMed
Publication date: 2025/09/24
Ke BingbingMao LinfeiHu MuCui YaqiChen MingWu CuipingGuan RuiruiYin ShankaiLi Chunyan - Fibroblasts, one of the core cellular components of peripheral nerves, play a pivotal role during peripheral nerve regeneration; however, whether extracellular vesicles (EVs) derived from peripheral nerve fibroblasts promote nerve regeneration remains unclear. In this study, we first demonstrated that EVs derived from peripheral nerve fibroblasts (fibroblasts-EVs) significantly promoted the growth and regeneration of motor and sensory neurons . In order to assess the application of fibroblasts-EVs in nerve grafting, we constructed a chitosan-based, fibroblast-EV-loaded nerve guidance conduit (NGC) and utilized it to bridge a 12-mm long sciatic nerve defect in rats. A series of functional and morphological assessments showed that EV-loaded NGCs significantly accelerated the recovery of sensory, motor, and electrophysiological functions, stimulated the growth and remyelination of regenerated axons, and alleviated denervation-induced atrophy of target muscles. To elucidate the underlying molecular mechanisms, we screened miRNAs enriched in fibroblast-EVs through miRNA sequencing. Among these miRNAs, miR-143-3p with the highest abundance was identified as a potential regulator of axon regeneration. Further investigations revealed that miR-143-3p promoted nerve regeneration by targeting Limk1, a negative regulator of axonal growth. This study expands our understanding of the role of fibroblasts in peripheral nerve regeneration and suggests that our developed bioactive material-based NGCs may present a promising design of tissue-engineered nerve grafts for peripheral nerve repair. - Source: PubMed
Publication date: 2026/07/14
Shen DingdingHe JiahuiYu MiaomeiCheng ZhenghangLiu JingyaZhao YueWang ShiranPei RuoyuDing FeiHe Qianru - p21-activated kinase 4 (PAK4), a critical effector of Ras homologous (Rho) GTP hydrolases (GTPases), promotes tumor progression and confers resistance to therapy by regulating malignant cellular phenotypes-such as proliferation, metastasis, and evasion of apoptosis-as well as by remodeling the tumor microenvironment (TME). Within tumor cells, PAK4 promotes proliferation by activating phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways. It enhances invasive and metastatic potential through cytoskeletal reorganization mediated by phosphorylation of effector proteins such as LIM domain kinase 1 (LIMK1)/cofilin and actin nucleation-promoting factor WASL (N-WASP). Furthermore, PAK4 facilitates immune evasion by stabilizing programmed cell death ligand 1 (PD-L1) and inhibiting pyroptosis. At the TME level, PAK4 is activated by hypoxia-inducible factor 1-alpha (HIF-1α), inflammatory cytokines, and extracellular matrix (ECM) stiffness. This activation reprograms the immune landscape, induces aberrant angiogenesis, and promotes metabolic acidosis via the Warburg effect, collectively fostering an immunosuppressive and therapy-resistant niche. Small-molecule PAK4 inhibitors (e.g., KPT-9274, PF-3758309, compound 55) and degraders (e.g., CPS-021) effectively suppress tumor growth in preclinical models. Combining these agents with immune checkpoint blockade, chemotherapy, or radiotherapy reverses therapy resistance and reprograms the TME. Elevated PAK4 expression correlates significantly with poor patient prognosis and resistance to immunotherapy, positioning it as both a predictive biomarker and a promising therapeutic target. Elucidating the PAK4-TME axis provides a mechanistic foundation for developing novel combinatorial strategies targeting the tumor microenvironment. - Source: PubMed
Publication date: 2026/07/23
Wang YimingOtkur WuxiyarCheng MaoshengWang HanxunXia Mingyu