Vaccination Against Receptor for Advanced Glycation End Products Attenuates the Progression of Diabetic Kidney Disease

Azegami, Tatsuhiko; Nakayama, Takashin; Hayashi, Kaori; Hishikawa, Akihito; Yoshimoto, Norifumi; Nakamichi, Ran; Itoh, Hiroshi

doi:10.2337/db20-1257

Cited by 21 publications

(10 citation statements)

References 45 publications

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“…Any remaining mannose in the system is mainly utilized for nonenzymatic glycation, the activity of which has been found to be five times that of glucose ( Sharma et al, 2014 ). Advanced glycation end products participate in the progression of DKD through multiple modes of action ( Vlassara et al, 2012 ; Azegami et al, 2021 ). Moreover, in our study, we found that isomaltose, D-mannose, and glucose were highly associated with differential genera of the microbiota.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease

et al. 2022

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Disturbance of circulating metabolites and disorders of the gut microbiota are involved in the progression of diabetic kidney disease (DKD). However, there is limited research on the relationship between serum metabolites and gut microbiota, and their involvement in DKD. In this study, using an experimental DKD rat model induced by combining streptozotocin injection and unilateral nephrectomy, we employed untargeted metabolomics and 16S rRNA gene sequencing to explore the relationship between the metabolic profile and the structure and function of gut microbiota. Striking alterations took place in 140 serum metabolites, as well as in the composition and function of rat gut microbiota. These changes were mainly associated with carbohydrate, lipid, and amino acid metabolism. In these pathways, isomaltose, D-mannose, galactonic acid, citramalic acid, and prostaglandin B2 were significantly upregulated. 3-(2-Hydroxyethyl)indole, 3-methylindole, and indoleacrylic acid were downregulated and were the critical metabolites in the DKD model. Furthermore, the levels of these three indoles were restored after treatment with the traditional Chinese herbal medicine Tangshen Formula. At the genera level, g_Eubacterium_nodatum_group, g_Lactobacillus, and g_Faecalibaculum were most involved in metabolic disorders in the progression of DKD. Notably, the circulating lipid metabolites had a strong relationship with DKD-related parameters and were especially negatively related to the mesangial matrix area. Serum lipid indices (TG and TC) and UACR were directly associated with certain microbial genera. In conclusion, the present research verified the anomalous circulating metabolites and gut microbiota in DKD progression. We also identified the potential metabolic and microbial targets for the treatment of DKD.

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Section: Discussionmentioning

confidence: 99%

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease

et al. 2022

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“…Advanced glycation end products (AGEs) are produced via the nonenzymatic glycation reaction and are considered major pathogenic factors that trigger vascular complications in diabetes ( Azegami et al, 2021 ). Incubation with 5 or 10 μg/ml berberine significantly inhibited AGE formation in high-glucose-AGEs-induced micro-endothelial injuries ( Hao et al, 2011 ).…”

Section: Effects Of Berberine On Vascular Diseasesmentioning

confidence: 99%

“…Similarly, 25 μM berberine had protective effects against endothelial injury by attenuating the generation of ROS, cellular apoptosis, NF-κB activation, and expression of adhesion molecules, which were induced by high glucose levels; it also enhanced the endothelium- dependent vasodilatation through the activation of the AMPK pathway (Wang et al, 2009). Advanced glycation end products (AGEs) are produced via the nonenzymatic glycation reaction and are considered major pathogenic factors that trigger vascular complications in diabetes (Azegami et al, 2021). Incubation with 5 or 10 μg/ml berberine significantly inhibited AGE formation in high-glucose-AGEs-induced micro-endothelial injuries (Hao et al, 2011).…”

Section: Diabetes Mellitusmentioning

confidence: 99%

Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases

Peng

et al. 2021

Front. Pharmacol.

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Traditional Chinese medicine plays a significant role in the treatment of various diseases and has attracted increasing attention for clinical applications. Vascular diseases affecting vasculature in the heart, cerebrovascular disease, atherosclerosis, and diabetic complications have compromised quality of life for affected individuals and increase the burden on health care services. Berberine, a naturally occurring isoquinoline alkaloid form Rhizoma coptidis, is widely used in China as a folk medicine for its antibacterial and anti-inflammatory properties. Promisingly, an increasing number of studies have identified several cellular and molecular targets for berberine, indicating its potential as an alternative therapeutic strategy for vascular diseases, as well as providing novel evidence that supports the therapeutic potential of berberine to combat vascular diseases. The purpose of this review is to comprehensively and systematically describe the evidence for berberine as a therapeutic agent in vascular diseases, including its pharmacological effects, molecular mechanisms, and pharmacokinetics. According to data published so far, berberine shows remarkable anti-inflammatory, antioxidant, antiapoptotic, and antiautophagic activity via the regulation of multiple signaling pathways, including AMP-activated protein kinase (AMPK), nuclear factor κB (NF-κB), mitogen-activated protein kinase silent information regulator 1 (SIRT-1), hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), janus kinase 2 (JAK-2), Ca2+ channels, and endoplasmic reticulum stress. Moreover, we discuss the existing limitations of berberine in the treatment of vascular diseases, and give corresponding measures. In addition, we propose some research perspectives and challenges, and provide a solid evidence base from which further studies can excavate novel effective drugs from Chinese medicine monomers.

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“…After incubation for 1.5 h at room temperature and subsequent washing with PBS-T, color was developed by using the TMB Microwell peroxidase substrate system (Kirkegaard & Perry Laboratories, Gaithersburg, MD, USA), and the optical density at 450 nm (OD450) was determined by a microplate reader (Cytation 5; BioTek, Winooski, VT, USA). The endpoint titer was expressed as the reciprocal log of the last dilution that gave an OD450 that was 0.1 units greater than that of the negative control 49 .…”

Section: Methodsmentioning

confidence: 99%

Vaccination against connective tissue growth factor attenuates the development of renal fibrosis

Nakayama

Azegami

Hayashi

et al. 2022

Sci Rep

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There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to attenuate the development of renal fibrosis. Three inoculations with this CTGF vaccine at 2-week intervals elicited antibodies specifically binding to human full-length CTGF, and the antigen-specific serum IgG antibody titers were maintained for > 30 weeks. The efficacy of the CTGF vaccine on renal fibrosis was evaluated in adenine-induced CKD and unilateral ureteral obstruction (UUO) murine models. In adenine-induced CKD model, immunization with the CTGF vaccine attenuated renal interstitial fibrosis. Vaccinated mice showed low levels of serum creatinine and urea nitrogen and low urine albumin–creatinine ratio compared with vehicle-treated mice. In UUO model, the CTGF vaccination also suppressed the onset of renal fibrosis. In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and transforming growth factor-β-induced α-smooth muscle actin expression in kidney fibroblasts. These results demonstrate that the CTGF vaccine is a promising strategy to attenuate the development of renal fibrosis.

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Vaccination Against Receptor for Advanced Glycation End Products Attenuates the Progression of Diabetic Kidney Disease

Cited by 21 publications

References 45 publications

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease

Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases

Vaccination against connective tissue growth factor attenuates the development of renal fibrosis

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