A downstream molecule of 1,25-dihydroxyvitamin D3, alpha-1-acid glycoprotein, protects against mouse model of renal fibrosis

Bi, Jianzhong; Watanabe, Hiroshi; Fujimura, Rui; Nishida, Kimiaki; Nakamura, Ryota; Oshiro, Shun; Imafuku, Tadashi; Komori, Hisakazu; Miyahisa, Masako; Tanaka, Motoko; Matsushita, Kazutaka; Maruyama, Toru

doi:10.1038/s41598-018-35339-x

Cited by 23 publications

(27 citation statements)

References 33 publications

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“…This is supported by our recent study in which exogenously administered hAGP suppressed unilateral ureter obstruction-induced renal fibrosis in a mouse model. 27 Administration of hAGP inhibited the urinary albumin in ADR mice between day 7 and 21.…”

Section: Discussionmentioning

confidence: 97%

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α1-Acid Glycoprotein Attenuates Adriamycin-Induced Nephropathy via CD163 Expressing Macrophage Induction

et al. 2020

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Background: Recent clinical studies have shown that proteinuria is a critical factor in the progression of chronic kidney disease (CKD) and onset of cardiovascular disease (CVD). Inflammation and infiltration of macrophages into renal tissue are implicated as a cause of proteinuria. α1-acid glycoprotein (AGP), an acute phase plasma protein, is leaked into the urine in the patients with proteinuria. However, the relationship among the urinary leakage of AGP, renal inflammation and proteinuria remains unclear. Methods: Human AGP (hAGP) was exogenously administrated for five consecutive days to adriamycin-induced nephropathy model mice. Results: Adriamycin treatment increased urinary AGP accompanied by decreasing plasma AGP in mice. Exogenous hAGP administration to adriamycin-treated mice suppressed proteinuria, renal histological injury and inflammation. Then, hAGP administration increased renal CD163 expression, a marker of anti-inflammatory macrophages. Similar changes was observed in phorbol 12-myristate 13-acetatedifferentiated THP-1 cells treated with hAGP. Even in the presence of lipopolysaccharide, hAGP treatment increased CD163/IL-10 expression in differentiated THP-1 cells. Conclusions: AGP alleviates proteinuria and renal injury in mice with proteinuric kidney disease via induction of CD163-expressing macrophages with anti-inflammatory function. The results demonstrate that endogenous AGP could work to protect against glomerulus disease. Thus, AGP supplementation could be a possible new therapeutic intervention for patients with glomerular disease.

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Section: Discussionmentioning

confidence: 97%

“…The eluted sample was dialyzed against distilled water at 4 ºC, freeze-dried and stored at -20 ºC. 27 The purity of hAGP was confirmed by SDS-PAGE. The secondary structure of hAGP was confirmed by Circular dichroism.…”

Section: Purification Of Agpmentioning

confidence: 99%

α1-Acid Glycoprotein Attenuates Adriamycin-Induced Nephropathy via CD163 Expressing Macrophage Induction

et al. 2020

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“…Figure 9 depicts histology characteristics in different treatment groups for H&E staining. The ligated kidney in UUO mice showed apparent tubular dilation, lumen disappear, fibrosis, and increased inflammatory cells [31]. After treating with Em-MNPs, the manifestation of ligated kidney was significantly alleviated, which characterized as decreased inflammation cells and less matrix accumulation in the tubulointerstitium.…”

Section: Pharmacodynamics Studymentioning

confidence: 95%

Mesoscale nanoparticles encapsulated with emodin for targeting antifibrosis in animal models

et al. 2020

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The aim of this study is to explore the kidney-targeting capability of mesoscale nanoparticles (MNPs)-emodin (Em-MNPs) and its potential antifibrosis in the animal model. First, MNPs and Em-MNPs were synthesized via nanoprecipitation method, and their diameters were both ∼400 nm with the uniform size. The entrapment efficiency of MNPs was 45.1% when adding emodin at the concentration of 12 mg/mL. Moreover, cytotoxicity assay showed that Em-MNPs presented excellent biocompatibility in rat proximal tubular cells. Cellular uptake assay demonstrated that Em-MNPs had high-efficiency uptake, especially in the cytoplasm. Ex vivo organ fluorescence imaging revealed that Em-MNPs possessed specific kidney-targeting ability with relative long retention time in the kidney (∼24 h). In the renal unilateral ureteral obstruction model, Em-MNPs treatment could significantly alleviate kidney tubule injury and reduce extracellular matrix deposition compared with free MNPs. Herein, Em-MNPs with specific kidney-targeting and preferable antifibrosis effects in animal model may pave an avenue for treating renal diseases.

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“…Total RNA from kidney or cells was isolated and quantitative RT-PCR measurements were performed using methods previously described (20). The primers used for mRNA detection are shown in Supplemental Table 2.…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

Advanced Oxidation Protein Products Contribute to Renal Tubulopathy via Perturbation of Renal Fatty Acids

et al. 2020

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BackgroundRenal proximal tubulopathy plays a crucial role in kidney disease, but its molecular mechanism is incompletely understood. Because proximal tubular cells consume a lot of energy during reabsorption, the relationship between fatty acids (FAs) and proximal tubulopathy has been attracting attention. The purpose of this study is to investigate the association between change in renal FA composition and tubulopathy.MethodsMice with cisplatin-induced nephrotoxicity were used as a model of AKI and 5/6-nephrectomized mice were used as a model of CKD. Renal FA composition in mice was measured by GC-MS. Human tubular epithelial cells (HK-2 cells) were used for in vitro studies.ResultsIn kidneys of AKI mice, increased stearic acid (C18:0) and decreased palmitic acid (C16:0) were observed, accompanied by increased expression of the long-chain FA elongase Elovl6. Similar results were also obtained in CKD mice. We show that C18:0 has higher tubular toxicity than C16:0 via induction of ER stress. Using adenovirus-expressing Elovl6 or siRNA for Elovl6 in HK-2 cells, we demonstrated that increased Elovl6 expression contributes to tubulopathy via increasing C18:0. Elovl6 knockout suppressed the increased serum creatinine levels, renal ER stress, and inflammation that would usually result after 5/6 nephrectomy. Advanced oxidation protein products (AOPPs), specifically an oxidized albumin, was found to induce Elovl6 via the mTORC1/SREBP1 pathway.ConclusionsAOPPs may contribute to renal tubulopathy via perturbation of renal FAs through induction of Elovl6. The perturbation of renal FAs induced by the AOPPs-Elovl6 system could be a potential target for the treatment of tubulopathy.

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A downstream molecule of 1,25-dihydroxyvitamin D3, alpha-1-acid glycoprotein, protects against mouse model of renal fibrosis

Cited by 23 publications

References 33 publications

α1-Acid Glycoprotein Attenuates Adriamycin-Induced Nephropathy via CD163 Expressing Macrophage Induction

α1-Acid Glycoprotein Attenuates Adriamycin-Induced Nephropathy via CD163 Expressing Macrophage Induction

Mesoscale nanoparticles encapsulated with emodin for targeting antifibrosis in animal models

Advanced Oxidation Protein Products Contribute to Renal Tubulopathy via Perturbation of Renal Fatty Acids

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