CRIP1 expression in monocytes related to hypertension

Schweigert, Olga; Adler, Julia; Langst, Nathalie; Aïssi, Dylan; Escobar, Jorge Duque; Tong, Teng; Müller, Christian; Trégouët, David‐Alexandre; Łukowski, Robert; Zeller, Tanja

doi:10.1042/cs20201372

Cited by 8 publications

(6 citation statements)

References 42 publications

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“…Indeed, we did find discrete changes in NO-GC and cGKI abundance in CRP4 negative VSMCs and at least partly also in the aorta, respectively, while other components of the pathway were not assessed in detail. In addition, lack of CRP4 might alter the expression of other genes relevant for Ca 2+ handling and may also induce changes in, for instance, highly related LIM proteins [57,104]. Similar compensatory mechanisms involving members of the CRP family have been identified in cardiac muscle [57] and the vasculature [65].…”

Section: Conclusion and Limitations Of The Studymentioning

confidence: 83%

Cyclic GMP-Dependent Regulation of Vascular Tone and Blood Pressure Involves Cysteine-Rich LIM-Only Protein 4 (CRP4)

Längst

Adler

Schweigert

et al. 2021

IJMS

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The cysteine-rich LIM-only protein 4 (CRP4), a LIM-domain and zinc finger containing adapter protein, has been implicated as a downstream effector of the second messenger 3′,5′-cyclic guanosine monophosphate (cGMP) pathway in multiple cell types, including vascular smooth muscle cells (VSMCs). VSMCs and nitric oxide (NO)-induced cGMP signaling through cGMP-dependent protein kinase type I (cGKI) play fundamental roles in the physiological regulation of vascular tone and arterial blood pressure (BP). However, it remains unclear whether the vasorelaxant actions attributed to the NO/cGMP axis require CRP4. This study uses mice with a targeted deletion of the CRP4 gene (CRP4 KO) to elucidate whether cGMP-elevating agents, which are well known for their vasorelaxant properties, affect vessel tone, and thus, BP through CRP4. Cinaciguat, a NO- and heme-independent activator of the NO-sensitive (soluble) guanylyl cyclase (NO-GC) and NO-releasing agents, relaxed both CRP4-proficient and -deficient aortic ring segments pre-contracted with prostaglandin F2α. However, the magnitude of relaxation was slightly, but significantly, increased in vessels lacking CRP4. Accordingly, CRP4 KO mice presented with hypotonia at baseline, as well as a greater drop in systolic BP in response to the acute administration of cinaciguat, sodium nitroprusside, and carbachol. Mechanistically, loss of CRP4 in VSMCs reduced the Ca2+-sensitivity of the contractile apparatus, possibly involving regulatory proteins, such as myosin phosphatase targeting subunit 1 (MYPT1) and the regulatory light chain of myosin (RLC). In conclusion, the present findings confirm that the adapter protein CRP4 interacts with the NO-GC/cGMP/cGKI pathway in the vasculature. CRP4 seems to be part of a negative feedback loop that eventually fine-tunes the NO-GC/cGMP axis in VSMCs to increase myofilament Ca2+ desensitization and thereby the maximal vasorelaxant effects attained by (selected) cGMP-elevating agents.

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Section: Conclusion and Limitations Of The Studymentioning

confidence: 83%

Cyclic GMP-Dependent Regulation of Vascular Tone and Blood Pressure Involves Cysteine-Rich LIM-Only Protein 4 (CRP4)

Längst

Adler

Schweigert

et al. 2021

IJMS

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“…A previous study demonstrated that IGFBP5 , 223 PRDX6 , 224 PKM (pyruvate kinase M1/2) , 225 PRDX1 , 226 and USP22 227 were more highly expressed in diabetic nephropathy. Durgin et al, 228 Zhang et al, 229 Hamada et al, 230 Gong et al, 231 Li et al, 232 Lin et al, 233 and Schweigert et al 234 suggested that CYB5R3, CACNA1A, GLCCI1, CAP1, HSP90AB1, BLVRA (biliverdinreductase A), and CRIP1 were involved in the progression of hypertension. These results suggested that these, cognitive impairment, cardiovascular diseases, obesity, diabetic nephropathy and hypertension responsible genes might influence the development of T2DM through the altered expression.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of Next Generation Sequencing Data Identifies Molecular Biomarkers Associated With Type 2 Diabetes Mellitus

Alur

Raju

Vastrad³

et al. 2023

Clin Med Insights Endocrinol Diabetes

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Background: Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder. The aim of the present investigation was to identify gene signature specific to T2DM. Methods: The next generation sequencing (NGS) dataset GSE81608 was retrieved from the gene expression omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs) between T2DM and normal controls. Then, Gene Ontology (GO) and pathway enrichment analysis, protein-protein interaction (PPI) network, modules, miRNA (micro RNA)-hub gene regulatory network construction and TF (transcription factor)-hub gene regulatory network construction, and topological analysis were performed. Receiver operating characteristic curve (ROC) analysis was also performed to verify the prognostic value of hub genes. Results: A total of 927 DEGs (461 were up regulated and 466 down regulated genes) were identified in T2DM. GO and REACTOME results showed that DEGs mainly enriched in protein metabolic process, establishment of localization, metabolism of proteins, and metabolism. The top centrality hub genes APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5, and SQSTM1 were screened out as the critical genes. ROC analysis provides prognostic value of hub genes. Conclusion: The potential crucial genes, especially APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5, and SQSTM1, might be linked with risk of T2DM. Our study provided novel insights of T2DM into genetics, molecular pathogenesis, and novel therapeutic targets.

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“…Cysteine-rich intestinal protein 1 (CRIP1), a LIM protein subfamily, contains a short LIM structural domain (Cai et al, 2017). CRIP1-positive circulating and splenic monocytes have been reported to play an important role in the inflammatory process associated with hypertension, and CRIP1 may influence the interaction of the immune system and the pathogenesis of hypertension (Schweigert et al, 2021). In addition, it can regulate the growth and differentiation of eukaryotic cells (Cai et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive bioinformatics analysis reveals biomarkers of DNA methylation-related genes in varicose veins

Liu²,

Liu³

et al. 2022

Front. Genet.

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Background: Patients with Varicose veins (VV) show no obvious symptoms in the early stages, and it is a common and frequent clinical condition. DNA methylation plays a key role in VV by regulating gene expression. However, the molecular mechanism underlying methylation regulation in VV remains unclear.Methods: The mRNA and methylation data of VV and normal samples were obtained from the Gene Expression Omnibus (GEO) database. Methylation-Regulated Genes (MRGs) between VV and normal samples were crossed with VV-associated genes (VVGs) obtained by weighted gene co-expression network analysis (WGCNA) to obtain VV-associated MRGs (VV-MRGs). Their ability to predict disease was assessed using receiver operating characteristic (ROC) curves. Biomarkers were then screened using a random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM). Next, gene set enrichment analysis (GSEA) was performed to explore the functions of biomarkers. Furthermore, we also predicted their drug targets, and constructed a competing endogenous RNAs (ceRNA) network and a drug target network. Finally, we verified their mRNA expression using quantitative real-time polymerase chain reaction (qRT-PCR).Results: Total three VV-MRGs, namely Wnt1-inducible signaling pathway protein 2 (WISP2), Cysteine-rich intestinal protein 1 (CRIP1), and Odd-skipped related 1 (OSR1) were identified by VVGs and MRGs overlapping. The area under the curves (AUCs) of the ROC curves for these three VV-MRGs were greater than 0.8. RF was confirmed as the optimal diagnostic model, and WISP2, CRIP1, and OSR1 were regarded as biomarkers. GSEA showed that WISP2, CRIP1, and OSR1 were associated with oxidative phosphorylation, extracellular matrix (ECM), and respiratory system functions. Furthermore, we found that lncRNA MIR17HG can regulate OSR1 by binding to hsa-miR-21-5p and that PAX2 might treat VV by targeting OSR1. Finally, qRT-PCR results showed that the mRNA expression of the three genes was consistent with the results of the datasets.Conclusion: This study identified WISP2, CRIP1, and OSR1 as biomarkers of VV through comprehensive bioinformatics analysis, and preliminary explored the DNA methylation-related molecular mechanism in VV, which might be important for VV diagnosis and exploration of potential molecular mechanisms.

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CRIP1 expression in monocytes related to hypertension

Cited by 8 publications

References 42 publications

Cyclic GMP-Dependent Regulation of Vascular Tone and Blood Pressure Involves Cysteine-Rich LIM-Only Protein 4 (CRP4)

Cyclic GMP-Dependent Regulation of Vascular Tone and Blood Pressure Involves Cysteine-Rich LIM-Only Protein 4 (CRP4)

Bioinformatics Analysis of Next Generation Sequencing Data Identifies Molecular Biomarkers Associated With Type 2 Diabetes Mellitus

Comprehensive bioinformatics analysis reveals biomarkers of DNA methylation-related genes in varicose veins

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