Identification of novel therapeutic targets for contrast induced acute kidney injury (CI-AKI): alpha blockers as a therapeutic strategy for CI-AKI

Kilari, Sreenivasulu; Sharma, Amit; Zhao, Chunrong; Singh, Avishek; Cai, Chuanqi; Simeon, Michael L.; Wijnen, André J. van; Misra, Sanjay

doi:10.1016/j.trsl.2021.03.005

Cited by 7 publications

(7 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tang et al 8 reported seven genes were associated with involvement in the occurrence and development of sepsisrelated AKI by bioinformatics analysis. Sreenivasulu et al 9 identified a novel therapeutic target Adra1b for contrast-induced acute kidney injury through bioinformatics methods and animal experiments.…”

Section: Introductionmentioning

confidence: 99%

“…Tang et al 8 reported seven genes were associated with involvement in the occurrence and development of sepsis‐related AKI by bioinformatics analysis. Sreenivasulu et al 9 identified a novel therapeutic target Adra1b for contrast‐induced acute kidney injury through bioinformatics methods and animal experiments. However, reports about AKI in critically ill patients were rare, it was very vital to explore novel and useful diagnostic biomarkers in transcriptome level.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comprehensive analysis of fifteen hub genes to identify a promising diagnostic model, regulated networks, and immune cell infiltration in acute kidney injury

Sun

Cao

Huang

et al. 2022

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Background Acute kidney injury is a common clinical problem with no sensitive and specific diagnostic biomarkers and definitive treatments. The underlying molecular mechanisms of acute kidney injury are unclear. Therefore, it is pivotal to explore the underlying mechanisms and screen for novel diagnostic biomarkers, and therapeutic targets. Methods The present study identified 15 hub genes by WGCNA analysis. LASSO‐based logistic regression analysis was used to select key features and construct a diagnostic model of AKI. In addition, GO and KEGG analyses were performed and TF‐mRNA and miRNA‐mRNA network analysis and immune infiltration analysis of hub genes were performed to reveal the underlying mechanisms of AKI. Results A diagnostic model was constructed by LASSO‐based logistic regression analysis and was validated by RT‐qPCR based on 15 hub genes. GO and KEGG analyses revealed DEGs were enriched in oxidation–reduction process, cell adhesion, proliferation, migration, and metabolic process. The enriched TFs were BRD2, EP300, ETS1, MYC, SPI1, and ZNF263. The enriched miRNAs were miR‐181c‐5p, miR‐218‐5p, miR‐485‐5p, miR‐532‐5p and miR‐6884‐5p. The immune infiltration analysis showed that Macrophages M2 was decreasing significantly revealing a protective factor for further AKI treatment. Conclusions The present study identified 15 hub genes based on WGCNA. Development and validation of a potentially diagnostic model based on 15 hub genes. In addition, exploring the interaction between transcriptional factors and 15 hub genes, and miRNA‐mRNA relationship pairs. Furthermore, immune infiltration analysis was performed by analyzing gene expression profiles of AKI. Our study provides some basis for further experimental studies.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of fifteen hub genes to identify a promising diagnostic model, regulated networks, and immune cell infiltration in acute kidney injury

Sun

Cao

Huang

et al. 2022

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

“…Genome-wide transcriptional profiling constitutes a powerful tool to analyze gene expression with a huge potential for identifying novel drug targets, improving current therapies and discovering biomarkers [1] , [2] . In particular, whole-blood transcriptomic analysis has gained importance in clinical research [3] .…”

Section: Introductionmentioning

confidence: 99%

Genome-wide transcriptional profiling of pulmonary functional sequelae in ARDS- secondary to SARS-CoV-2 infection

García-Hidalgo

Peláez

González

et al. 2022

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

“…Contrast media (CM) are widely used for imaging and invasive procedures in clinical, such as radiography, computed tomography, magnetic resonance imaging, and angiography. [1] However, with the wide use of CM, contrast-induced nephropathy (CIN) has been the third prevalent cause of all hospital-acquired acute kidney injury (AKI). [2][3][4] The incidence of CIN in low-risk population was 13.38%, [5] but increased up to 40%-50% in high-risk population with chronic renal insufficiency [6] and diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 99%

An in vivo and in vitro model on the protective effect of cilnidipine on contrast‐induced nephropathy via regulation of apoptosis and CaMKⅡ/mPTP pathway

Liu

Zhou

et al. 2022

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Contrast‐induced nephropathy (CIN) is an acute kidney injury (AKI) observed after the administration of contrast media. Calcium channel blockers (CCBs) have been reported to exert a renal protective effect. This study aims to investigate the role of cilnidipine, a novel CCBs, on CIN by regulating the calcium/calmodulin‐dependent protein kinase Ⅱ(CaMKⅡ)/mitochondrial permeability transition pore (mPTP) pathway. Here, iohexol, a representative contrast media, was used to establish CIN model. KN‐93 (CaMKⅡ inhibitor) and atractyloside (mPTP opener) were administered in rats, and CaMKⅡ overexpression was used in Human proximal tubular epithelial cells. Markers of renal injury (serum creatinine, blood urea nitrogen, and urinary NAGL), hematoxylin‐eosin stain, oxidative stress (ROS, superoxide dismutase [SOD], and malondialdehyde [MDA] levels), cell death (MTT and terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labeling [TUNEL]), mitochondrial function (mPTP, mitochondrial membrane potential [MMP], and ATP) were assessed. Western blots were used to measure the expression levels of Bax/Bcl‐2, caspase‐3, CaMKⅡ/mPTP signaling pathways. Results showed that cilnidipine markedly improved kidney function, and alleviated tubular cell apoptosis, oxidative stress and mitochondrial damage induced by iohexol in vitro and in vivo. The underlying mechanism may be that cilnidipine relieved CaMKⅡ activation and mPTP opening induced by iohexol. All of these protective effects of cilnidipine were attenuated by CaMKⅡ overexpression and atractyloside (mPTP opener) pretreatment. Moreover, KN‐93 (CaMKⅡ inhibitor) treatment showed a similar renal protective effect with cilnidipine, while the protective effect of cilnidipine on kidney in CIN rats was not further suppressed by KN‐93 cotreatment. These in vitro and in vivo results point toward the fact that cilnidipine might be a novel therapeutic drug against contrast‐induced nephrotoxicity in a CaMKⅡ‐dependent manner.

show abstract

Identification of novel therapeutic targets for contrast induced acute kidney injury (CI-AKI): alpha blockers as a therapeutic strategy for CI-AKI

Cited by 7 publications

References 41 publications

Comprehensive analysis of fifteen hub genes to identify a promising diagnostic model, regulated networks, and immune cell infiltration in acute kidney injury

Comprehensive analysis of fifteen hub genes to identify a promising diagnostic model, regulated networks, and immune cell infiltration in acute kidney injury

Genome-wide transcriptional profiling of pulmonary functional sequelae in ARDS- secondary to SARS-CoV-2 infection

An in vivo and in vitro model on the protective effect of cilnidipine on contrast‐induced nephropathy via regulation of apoptosis and CaMKⅡ/mPTP pathway

Contact Info

Product

Resources

About