<scp>MicroRNA</scp>‐17‐5p restrains the dysfunction of <scp>Ang‐II</scp> induced podocytes by suppressing secreted modular calcium‐binding protein 2 via <scp>NF‐κB</scp> and <scp>TGFβ</scp> signaling

Xu, Mingzhu; Yi, Mengqiu; Li, Na

doi:10.1002/tox.23136

Cited by 4 publications

(1 citation statement)

References 35 publications

(69 reference statements)

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“…Activated NF-κB further induces the production of various inflammatory mediators and inflammatory cytokines, such as monocyte chemokine-l (MCP-l) and interleukins (ILs). These cytokines trigger an immunological inflammatory response, which results in damage and depletion of podocytes, kidney injury, and the progression of MN [12].…”

Section: Introductionmentioning

confidence: 99%

PLA2G12B Mediates Arachidonic Acid Metabolism through Activation of the NF-κB Pathway to Promote Membrane Nephropathy

Fu,

Ping,

Guo

et al. 2023

Kidney Blood Press Res

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Introduction: The disruption of podocytes structure and function are the main pathological mechanism of membranous nephropathy (MN). Phospholipases A2, Group XII B (PLA2G12B) was reported involved in the regulation of MN by interfering with arachidonic acid (AA) metabolism, but there is a lack of sufficient evidence. In this study, we investigated the role and molecular mechanism of PLA2G12B in MN. Methods: C57BL/6 mice were used to established MN model to extract primary podocytes, then divided into control, model, si- Phospholipases A2 receptor (PLA2R), PLA2G12B, PLA2G12B+ si-PLA2R, PLA2G12B+nuclear factor kappa-B (NF-κB) inhibitor, PLA2G12B+ NF-κB inhibitor+si-PLA2R groups. Hematoxylin-Eosin (HE) staining and immunofluorescence were used to detect kidneys histological arrangement, serum levels of cholesterol related indices and AA. Genes and proteins associated with metabolism and inflammatory factors were detected by qRT-PCR, and western blot. Results: The results revealed that AA metabolites were activated in the MN model mice and the expression of PLA2G12B and NF-κB pathway levels were elevated. Besides, cellular experiments demonstrated that prostaglandin I2 (PGI2), thromboxane A2 (TXA2) and leukotriene B4 (LTB4) and NF-κB pathway were significantly increased in the PLA2G12B group. Also, PLA2G12B promotes apoptosis and suppresses cell activity in podocytes, and these effects could be antagonized by NF-κB inhibitors. Furthermore, with the inference of si-PLA2R, the NF-κB inhibitors’ effects were reversed. Conclusion: Promotional effects of PLA2G12B in primary MN are associated with the regulation of AA metabolism and NF-κB pathway.

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Section: Introductionmentioning

confidence: 99%

PLA2G12B Mediates Arachidonic Acid Metabolism through Activation of the NF-κB Pathway to Promote Membrane Nephropathy

Fu,

Ping,

Guo

et al. 2023

Kidney Blood Press Res

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microRNA-148a in Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Cardiomyocyte Apoptosis in Atrial Fibrillation by Inhibiting SMOC2

2022

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SMOC2 gene interacts with APOL1 in the development of end-stage kidney disease: A genome-wide association study

et al. 2022

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BackgroundSome but not all African-Americans (AA) who carry APOL1 nephropathy risk variants (APOL1) develop kidney failure (end-stage kidney disease, ESKD). To identify genetic modifiers, we assessed gene–gene interactions in a large prospective cohort of the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.MethodsGenotypes from 8,074 AA participants were obtained from Illumina Infinium Multi-Ethnic AMR/AFR Extended BeadChip. We compared 388 incident ESKD cases with 7,686 non-ESKD controls, using a two-locus interaction approach. Logistic regression was used to examine the effect of APOL1 risk status (using recessive and additive models), single nucleotide polymorphism (SNP), and APOL1*SNP interaction on incident ESKD, adjusting for age, sex, and ancestry. APOL1*SNP interactions that met the threshold of 1.0 × 10−5 were replicated in the Genetics of Hypertension Associated Treatment (GenHAT) study (626 ESKD cases and 6,165 controls). In a sensitivity analysis, models were additionally adjusted for diabetes status. We conducted additional replication in the BioVU study.ResultsTwo APOL1 risk alleles prevalence (recessive model) was similar in the REGARDS and GenHAT studies. Only one APOL1–SNP interaction, for rs7067944 on chromosome 10, ~10 KB from the PCAT5 gene met the genome-wide statistical threshold (Pinteraction = 3.4 × 10−8), but this interaction was not replicated in the GenHAT study. Among other relevant top findings (with Pinteraction < 1.0 × 10−5), a variant (rs2181251) near SMOC2 on chromosome six interacted with APOL1 risk status (additive) on ESKD outcomes (REGARDS study, Pinteraction =5.3 × 10−6) but the association was not replicated (GenHAT study, Pinteraction = 0.07, BioVU study, Pinteraction = 0.53). The association with the locus near SMOC2 persisted further in stratified analyses. Among those who inherited ≥1 alternate allele of rs2181251, APOL1 was associated with an increased risk of incident ESKD (OR [95%CI] = 2.27[1.53, 3.37]) but APOL1 was not associated with ESKD in the absence of the alternate allele (OR [95%CI] = 1.34[0.96, 1.85]) in the REGARDS study. The associations were consistent after adjusting for diabetes.ConclusionIn a large genome-wide association study of AAs, a locus SMOC2 exhibited a significant interaction with the APOL1 locus. SMOC2 contributes to the progression of fibrosis after kidney injury and the interaction with APOL1 variants may contribute to an explanation for why only some APOLI high-risk individuals develop ESKD.

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MicroRNA‐17‐5p restrains the dysfunction of Ang‐II induced podocytes by suppressing secreted modular calcium‐binding protein 2 via NF‐κB and TGFβ signaling

Cited by 4 publications

References 35 publications

PLA2G12B Mediates Arachidonic Acid Metabolism through Activation of the NF-κB Pathway to Promote Membrane Nephropathy

PLA2G12B Mediates Arachidonic Acid Metabolism through Activation of the NF-κB Pathway to Promote Membrane Nephropathy

microRNA-148a in Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Cardiomyocyte Apoptosis in Atrial Fibrillation by Inhibiting SMOC2

SMOC2 gene interacts with APOL1 in the development of end-stage kidney disease: A genome-wide association study

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