History of IgA Nephropathy Mouse Models

Wehbi, Batoul; Pascal, Virginie; Zawil, Lina; Cogné, Michel; Aldigier, Jean-Claude

doi:10.3390/jcm10143142

Cited by 9 publications

(8 citation statements)

References 60 publications

(76 reference statements)

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“…Increasing evidence has indicated the importance of the gut-kidney axis in IgA nephropathy. The existing experimental model provides scattered clues [32]. For example, α1KI mice showed increased IgA polymerization levels when they were transferred from a germ-free to a conventional immune stimulation condition [33].…”

Section: Discussionmentioning

confidence: 99%

Sustained release of Lactobacillus casei cell wall extract can induce a continuous and stable IgA deposition model

Wan

Wang

et al. 2022

The Journal of Pathology

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Mucosal immune regulation is considered a key aspect of immunopathogenesis of IgA nephropathy (IgAN). Direct experimental evidence clarifying the role of intestinal mucosa attributes in IgAN is lacking. In this study, a mouse model was established via multiple low‐dose intraperitoneal injections of Lactobacillus casei cell wall extract (LCWE) emulsified with Complete Freund's Adjuvant (CFA). We found continuous and stable deposition of IgA in glomerular mesangial areas, accompanying high circulating levels of IgA and IgA–IgG complexes. Expression of the key extracellular matrix components collagen IV and fibronectin also increased in the mesangial areas of LCWE‐induced mice. IgA+B220+ B‐cell proportion increased in the small intestine (SI), Peyer's patches, inguinal lymph nodes, spleen, and bone marrow. The intestinal barrier was dysfunctional in the LCWE‐induced mice, and consistent with this, higher levels of serum zonulin (namely prehaptoglobin‐2), a regulator of epithelial and endothelial barrier function, were observed in patients with IgAN. Hematoxylin and eosin staining results indicated that immune tissues such as liver, spleen, and lymph nodes showed an inflammatory response and focal lesions. Glucocorticoid methylprednisolone treatment could alleviate serum IgA and IgA–IgG complex levels and mesangial IgA deposition. Taken together, our results indicate that we have successfully constructed a mouse model with IgA deposition in the mesangial areas of the glomeruli and provide evidence for the connection between the intestinal barrier and elevated circulating IgA and IgA–IgG in IgAN. © 2022 The Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 99%

Sustained release of Lactobacillus casei cell wall extract can induce a continuous and stable IgA deposition model

Wan

Wang

et al. 2022

The Journal of Pathology

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“…The amplicon pools were prepared for sequencing, and the size and quantity of the amplicon library were assessed on an Agilent 2100 Bioanalyzer (Agilent, USA) and with the Library Quantification Kit for Illumina (Kapa Biosciences, Woburn, MA, USA), respectively. The libraries were sequenced on NovaSeq PE250 platform [11, 12].…”

Section: Methodsmentioning

confidence: 99%

“…The model of experimental IgAN was established by the immunity combination method of oral bovine serum albumin (BSA) (MedChemExpress, USA) administration and staphylococcal enterotoxin B (MedChemExpress, USA) injection [12][13][14]. In brief, pseudo-germfree mice (ABX mice) were randomly divided into four groups: the blank group (ABX 0 ), model group (half-dose immunity combination (ABX 1/2 ), 75% immunity combination (ABX 3/4 ), and full-dose immunity combination (ABX 1 ) group; each group included 6 animals.…”

Section: Animal Modelmentioning

confidence: 99%

Aberrant Gut Microbiome Contributes to Barrier Dysfunction, Inflammation, and Local Immune Responses in IgA Nephropathy

Tang

Xiao

et al. 2023

Kidney Blood Press Res

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Introduction Numerous research have shown that serum Gal-deficient (Gd)-IgA1 levels are increased in IgA nephropathy (IgAN) patients and these levels are a dangerous risk factor for IgAN.It has been reported that a relationship between the gut microbiota and IgAN.Whether the gut microbiota participates in the pathogenesis of IgAN was still controversial. Methods We evaluated changes in the gut flora and the levels of Gd-IgA1 in IgAN patients and healthy controls (HCs). We investigated the Gd-IgA1 levels in both blood and urine specimens. C57BL/6 mice were given a broad-spectrum antibiotic cocktail to deplete the endogenous gut flora. We established a model of IgAN in pseudosterile mice and investigated the expression of the markers of intestinal permeability, inflammation, and local immune responses. Results Studies have shown that the levels of certain gut flora differ between IgAN patients and HCs. Moreover, elevated Gd-IgA1 levels were found in both the serum and urine. Interestingly, Coprococcus, Dorea, Bifidobacterium, Blautia and Lactococcus, selected from 10 candidate biomarkers to predict risk in IgAN patients according to random forest analysis, were inversely associated with urinary Gd-IgA1 levels. Notably, the urine level of Gd-IgA1 could best distinguish IgAN patients from HCs. Additionally, the degree of kidney damage in pseudosterile mice with IgAN was more severe than that in mice with IgAN. Furthermore, the markers of intestinal permeability were significantly elevated in pseudosterile IgAN mice. Moreover, the inflammation responses (TLR4, MyD88, and NF-κB in intestinal and renal tissues; TNF-α and IL-6 in serum) and Local Immune Responses (BAFF and APRIL in intestinal tissue) were upregulated in pseudosterile IgAN mice. Conclusions The urine Gd-IgA1 level may be as a biomarker for the early screening of potential IgAN, and Gut microbiota dysbiosis was demonstrated in IgAN, which might be involved the dysfunction of the mucosal barrier, inflammation and local Immune responses.

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“…It has been demonstrated that oxidative stress-induced protein oxidation and lipid peroxidation is one of the underlying pathogenic mechanisms [ 165 , 166 , 167 , 168 , 169 ]. While animal models of IgAN are available for studying the pathogenesis of IgAN and exploring therapeutic approaches [ 170 , 171 ], the potential effects of ALA in this kidney disorder have not been evaluated. Nonetheless, it is conceivable that ALA would exhibit nephroprotective effects in IgAN, given its powerful antioxidant capacity.…”

Section: Miscellaneousmentioning

confidence: 99%

Renal-Protective Roles of Lipoic Acid in Kidney Disease

Kamt

Liu

2023

Nutrients

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The kidney is a crucial organ that eliminates metabolic waste and reabsorbs nutritious elements. It also participates in the regulation of blood pressure, maintenance of electrolyte balance and blood pH homeostasis, as well as erythropoiesis and vitamin D maturation. Due to such a heavy workload, the kidney is an energy-demanding organ and is constantly exposed to endogenous and exogenous insults, leading to the development of either acute kidney injury (AKI) or chronic kidney disease (CKD). Nevertheless, there are no therapeutic managements to treat AKI or CKD effectively. Therefore, novel therapeutic approaches for fighting kidney injury are urgently needed. This review article discusses the role of α-lipoic acid (ALA) in preventing and treating kidney diseases. We focus on various animal models of kidney injury by which the underlying renoprotective mechanisms of ALA have been unraveled. The animal models covered include diabetic nephropathy, sepsis-induced kidney injury, renal ischemic injury, unilateral ureteral obstruction, and kidney injuries induced by folic acid and metals such as cisplatin, cadmium, and iron. We highlight the common mechanisms of ALA’s renal protective actions that include decreasing oxidative damage, increasing antioxidant capacities, counteracting inflammation, mitigating renal fibrosis, and attenuating nephron cell death. It is by these mechanisms that ALA achieves its biological function of alleviating kidney injury and improving kidney function. Nevertheless, we also point out that more comprehensive, preclinical, and clinical studies will be needed to make ALA a better therapeutic agent for targeting kidney disorders.

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History of IgA Nephropathy Mouse Models

Cited by 9 publications

References 60 publications

Sustained release of Lactobacillus casei cell wall extract can induce a continuous and stable IgA deposition model

Sustained release of Lactobacillus casei cell wall extract can induce a continuous and stable IgA deposition model

Aberrant Gut Microbiome Contributes to Barrier Dysfunction, Inflammation, and Local Immune Responses in IgA Nephropathy

Renal-Protective Roles of Lipoic Acid in Kidney Disease

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