Proteomics analysis of liver pathological calcification suggests a role for the IQ motif containing GTPase activating protein 1 in myofibroblast function

2009 ◽  
Vol 3 (3) ◽  
pp. 307-321 ◽  
Author(s):  
Fariba Kalantari ◽  
Patrick Auguste ◽  
Tahereh Ziafazeli ◽  
George Tzimas ◽  
Lars Malmström ◽  
...  
PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0129314 ◽  
Author(s):  
Amr M. Ghaleb ◽  
Agnieszka B. Bialkowska ◽  
Ashley J. Snider ◽  
Dmitri V. Gnatenko ◽  
Yusuf A. Hannun ◽  
...  

2017 ◽  
Vol 493 (4) ◽  
pp. 1384-1389
Author(s):  
Norimichi Itoh ◽  
Taku Nagai ◽  
Takashi Watanabe ◽  
Kentaro Taki ◽  
Toshitaka Nabeshima ◽  
...  

2019 ◽  
Author(s):  
Makoto Tanaka ◽  
Tomohiro Osanai ◽  
Yoshimi Homma ◽  
Kenji Hanada ◽  
Ken Okumura ◽  
...  

AbstractPhospholipase C (PLC)-δ1, activated by p122RhoGTPase-activating protein (GAP)/deleted in liver cancer-1 (p122RhoGAP/DLC-1), contributes to the coronary spastic angina (CSA) pathogenesis. The present study aims to further investigate the p122RhoGAP/DLC-1 protein. We examined molecules assisting this protein and identified a scaffold protein—IQ motif-containing GTPase-activating protein 1 (IQGAP1). IQGAP1-C binds to the steroidogenic acute regulatory-related lipid transfer (START) domain of p122RhoGAP/DLC-1, and PLC-δ1 binds to IQGAP1-N, forming a complex. In fluorescence microscopy, small dots of PLC-δ1 created fine linear arrays like microtubules, and IQGAP1 and p122RhoGAP/DLC-1 were colocated in the cytoplasm with PLC-δ1. Ionomycin induced the raft recruitment of the PLC-δ1, IQGAP1, and p122RhoGAP/DLC-1 complex by translocation to the plasma membrane (PM), indicating the movement of this complex is along microtubules with the motor protein kinesin. Moreover, the IQGAP1 protein was elevated in skin fibroblasts obtained from patients with CSA, and it enhanced the PLC activity and peak intracellular calcium concentration in response to acetylcholine. IQGAP1, a novel stimulating protein, forms a complex with p122RhoGAP/DLC-1 and PLC-δ1 that moves along microtubules and enhances the PLC activity.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mengyin Chen ◽  
Siliang Chen ◽  
Dan Yang ◽  
Jiawei Zhou ◽  
Bao Liu ◽  
...  

BackgroundSurface rupture of carotid plaque can cause severe cerebrovascular disease, including transient ischemic attack and stroke. The aim of this study was to elucidate the molecular mechanism governing carotid plaque progression and to provide candidate treatment targets for carotid atherosclerosis.MethodsThe microarray dataset GSE28829 and the RNA-seq dataset GSE104140, which contain advanced plaque and early plaque samples, were utilized in our analysis. Differentially expressed genes (DEGs) were screened using the “limma” R package. Gene modules for both early and advanced plaques were identified based on co-expression networks constructed by weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) analyses were employed in each module. In addition, hub genes for each module were identified. Crucial genes were identified by molecular complex detection (MCODE) based on the DEG co-expression network and were validated by the GSE43292 dataset. Gene set enrichment analysis (GSEA) for crucial genes was performed. Sensitivity analysis was performed to evaluate the robustness of the networks that we constructed.ResultsA total of 436 DEGs were screened, of which 335 were up-regulated and 81 were down-regulated. The pathways related to inflammation and immune response were determined to be concentrated in the black module of the advanced plaques. The hub gene of the black module was ARHGAP18 (Rho GTPase activating protein 18). NCF2 (neutrophil cytosolic factor 2), IQGAP2 (IQ motif containing GTPase activating protein 2) and CD86 (CD86 molecule) had the highest connectivity among the crucial genes. All crucial genes were validated successfully, and sensitivity analysis demonstrated that our results were reliable.ConclusionTo the best of our knowledge, this study is the first to combine DEGs and WGCNA to establish a DEG co-expression network in carotid plaques, and it proposes potential therapeutic targets for carotid atherosclerosis.


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