Disparate roles of retinoid acid signaling molecules in kidney disease

Chen, Anqun; Liu, Yu; Lu, Yu; Lee, Kyung Hwa; He, John Cijiang

doi:10.1152/ajprenal.00045.2021

Cited by 24 publications

(18 citation statements)

References 76 publications

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“…Chen et al revealed that retinoic acid receptor responder protein 1, which is mainly restricted to podocytes, upregulates in the glomerular of the chronic nephrosis patients. Inversely, lower Rarres1 improved Adriamycin-induced nephropathy in the inducible RARRES1 knockdown mice [ 12 ]. By using a rodent FSGS model induced by Adriamycin, Qi et al suggested that miR-150 inhibitor exerts protective effect on the glomerular via ameliorating renal fibrosis and inflammation [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Decoding the Mechanism behind the Pathogenesis of the Focal Segmental Glomerulosclerosis

Zhu

Tang

Mao

et al. 2022

Computational and Mathematical Methods in Medicine

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Focal segmental glomerulosclerosis (FSGS) is a chronic glomerular disease associated with podocyte injury which is named after the pathologic features of the kidney. The aim of this study is to decode the key changes in gene expression and regulatory network involved in the formation of FSGS. Integrated network analysis included Gene Expression Omnibus (GEO) datasets to identify differentially expressed genes (DEGs) between FSGS patients and healthy donors. Bioinformatics analysis was used to identify the roles of the DEGs and included the development of protein-protein interaction (PPI) networks, Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and the key modules were assured. The expression levels of DEGs were validated using the additional dataset. Eventually, transcription factors and ceRNA networks were established to illuminate the regulatory relationships in the formation of FSGS. 1130 DEGs including 475 upregulated genes and 655 downregulated genes with functional enrichment analysis were determined. Further analysis uncovered that the validated hub genes were defined as candidate genes, including Complement C3a Receptor 1 (C3AR1), C-C Motif Chemokine Receptor 1(CCR1), C-X3-C Motif Chemokine Ligand 1 (CX3CL1), Melatonin Receptor 1A (MTNR1A), and Purinergic Receptor P2Y13 (P2RY13). More importantly, we identified transcription factors and mRNA-miRNA-lncRNA regulatory networks associated with the candidate genes. The candidate genes and regulatory networks discovered in this study can help to comprehend the molecular mechanism of FSGS and supply potential targets for the diagnosis and therapy of FSGS.

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Section: Introductionmentioning

confidence: 99%

Decoding the Mechanism behind the Pathogenesis of the Focal Segmental Glomerulosclerosis

Zhu

Tang

Mao

et al. 2022

Computational and Mathematical Methods in Medicine

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“…It is reported that activation of the RARα reduces lung inflammation in mice by inhibiting the transcription of inflammatory cytokines ( 48 ). In kidney disease, the activation of RARα confers renal protection by inducing podocyte differentiation and by inhibiting proliferation and inflammation ( 49 ). RARα also represents a promising potential therapeutic target in neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Activation of RARα Receptor Attenuates Neuroinflammation After SAH via Promoting M1-to-M2 Phenotypic Polarization of Microglia and Regulating Mafb/Msr1/PI3K-Akt/NF-κB Pathway

Tian

Liu

et al. 2022

Front. Immunol.

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Background and PurposeSubarachnoid hemorrhage (SAH) is a life-threatening subtype of stroke with high rates of mortality. In the early stages of SAH, neuroinflammation is one of the important mechanisms leading to brain injury after SAH. In various central nervous system diseases, activation of RARα receptor has been proven to demonstrate neuroprotective effects. This study aimed to investigate the anti-inflammatory effects of RARα receptor activation after SAH.MethodsInternal carotid artery puncture method used to established SAH model in Sprague-Dawley rats. The RARα specific agonist Am80 was injected intraperitoneally 1 hour after SAH. AGN196996 (specific RARα inhibitor), Msr1 siRNA and LY294002 (PI3K-Akt inhibitor) were administered via the lateral ventricle before SAH. Evaluation SAH grade, neurological function score, blood-brain barrier permeability. BV2 cells and SH-SY5Y cells were co-cultured and stimulated by oxyhemoglobin to establish an in vitro model of SAH. RT-PCR, Western blotting, and immunofluorescence staining were used to investigate pathway-related proteins, microglia activation and inflammatory response. Results: The expression of RARα, Mafb, and Msr1 increased in rat brain tissue after SAH. Activation of the RARα receptor with Am80 improved neurological deficits and attenuated brain edema, blood brain barrier permeability. Am80 increased the expression of Mafb and Msr1, and reduced neuroinflammation by enhancing the phosphorylation of Akt and by inhibiting the phosphorylation of NF-κB. AGN196996, Msr1 siRNA, and LY294002 reversed the therapeutic effects of Am80 by reducing the expression of Msr1 and the phosphorylation of Akt. In vitro model of SAH, Am80 promoted M1-to-M2 phenotypic polarization in microglia and suppressed the nuclear transcription of NF-κB.ConclusionActivation of the RARα receptor attenuated neuroinflammation by promoting M1-to-M2 phenotypic polarization in microglia and regulating the Mafb/Msr1/PI3K-Akt/NF-κB pathway. RARα might serve as a potential target for SAH therapy.

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“…Rats with pumpkin in their diet had definitely higher supply of vitamins A and E than did those receiving the standard diet, and excessive amounts of these vitamins can lead to glomerular hyperfiltration and hypercalcemia [ 43 ]. The biologically active form of vitamin A is retinoic acid, which can lead to the progression of glomerular disease [ 44 , 45 ]. However, in this study, the vitamin levels in blood and tissues were not measured; hence, the above explanation for the negative effects of fortified pumpkin on the kidneys is only speculation.…”

Section: Discussionmentioning

confidence: 99%

Effects of Calcium Lactate-Enriched Pumpkin on Calcium Status in Ovariectomized Rats

Wawrzyniak

Gramza‐Michałowska

Pruszyńska‐Oszmałek

et al. 2022

Foods

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This study aimed to evaluate the effects of enriched pumpkin on calcium status in ovariectomized rats. The study was conducted in sixty female Wistar rats, which were divided into six groups: a group fed a standard diet (C) and five ovariectomized groups fed a standard diet (OVX_C) or a diet with calcium lactate (CaL), with calcium lactate-enriched pumpkin (P_CaL), with calcium lactate and alendronate (CaL_B), or with calcium lactate-enriched pumpkin with alendronate (P_CaL_B). After 12 weeks of the intervention, the rats were sacrificed, and their blood and tissues were collected. The calcium concentrations in serum and in tissues were measured using flame atomic absorption spectrometry (AAS). Serum concentrations of procollagen type-1 amino-terminal propeptide (PINP), parathyroid hormone PTH, estrogen (ES), and osteocalcin (OC) were determined with enzyme-linked immunosorbent assay (ELISA). It was found that enriched pumpkin increased the calcium level in the kidneys (194.13 ± 41.01 mg) compared to the C (87.88 ± 12.42 mg) and OVX_C (79.29 ± 7.66 mg) groups. The addition of alendronate increased the calcium level in the femurs (267.63 ± 23.63 mg) and more than six times in the kidneys (541.33 ± 62.91 mg) compared to the OVX_C group (234.53 ± 21.67 mg and 87.88 ± 12.42 mg, respectively). We found that the CaL, P_CaL, and CaL_B groups had significantly lower PINP serum concentrations (4.45 ± 0.82 ng/mL, 4.14 ± 0.69 ng/mL, and 3.77 ± 0.33 ng/mL) and higher PTH serum levels (3.39 ± 0.54 ng/dL, 3.38 ± 0.57 ng/dL, and 3.47 ± 0.28 ng/dL) than the OVX_C group (4.69 ± 0.82 ng/mL and 2.59 ± 0.45 ng/dL, respectively). In conclusion, pumpkin enriched with calcium lactate affects calcium status and normalizes PINP and PTH serum levels in ovariectomized rats. Diet with enriched pumpkin and alendronate increase calcium concentration in the femur. Enriched pumpkin causes calcium to accumulate in the kidneys of ovariectomized rats; alendronate significantly exacerbates this effect.

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Disparate roles of retinoid acid signaling molecules in kidney disease

Cited by 24 publications

References 76 publications

Decoding the Mechanism behind the Pathogenesis of the Focal Segmental Glomerulosclerosis

Decoding the Mechanism behind the Pathogenesis of the Focal Segmental Glomerulosclerosis

Activation of RARα Receptor Attenuates Neuroinflammation After SAH via Promoting M1-to-M2 Phenotypic Polarization of Microglia and Regulating Mafb/Msr1/PI3K-Akt/NF-κB Pathway

Effects of Calcium Lactate-Enriched Pumpkin on Calcium Status in Ovariectomized Rats

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