Additive effect of PPAR-γ agonist and ARB in treatment of experimental IgA nephropathy

Lai, Kar Neng; Chan, Loretta Y.Y.; Guo, Hong; Tang, Sydney C.W.; Leung, Joseph C.K.

doi:10.1007/s00467-010-1703-y

Cited by 25 publications

(23 citation statements)

References 30 publications

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“…As no ddY mouse was available in China, we used the animal IgAN model in which a direct antigenic stimulus to esophageal endothelial mucosal cells activates local and migratory macrophages was based on our previous studies [28] . Data from other studies have also shown that this method can build a good stable animal model for IgAN [29,30] . IgAN was induced by continuous oral immunization with 0.1% BSA (G7516, Sigma Chemical Co., St. Louis, Mo., USA) with 6 m M HCl in tap water for 10 weeks, followed by tail intravenous injection of 1 mg BSA daily for 3 successive days.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

He¹,

Peng²,

Wang³

et al. 2015

Am J Nephrol

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Background: Immunoglobulin class-switch recombination (CSR) is crucial for the expression of IgA, and it plays a vital role in the physiopathology of IgA nephropathy (IgAN). The aim of the study is to investigate the effect of polyriboinosinic:polyribocytidylic acid (poly(I:C)) in modulating toll-like receptor (TLR) 3-B-cell-activating factor belonging to the TNF family (BAFF) axis activation, which in turn promotes IgA CSR of IgAN patients and the IgAN rat model. Methods: Blood samples and tonsillar tissue specimens were obtained from 24 patients with IgAN and 26 patients with chronic tonsillitis as control. We also used the IgAN rat model to investigate the relationship between viral infection and IgA CSR. Results: Immunohistochemical and ELISA western blotting examination revealed that the TLR3/BAFF axis is activated in IgAN patients when compared to controls. Synthetic double-stranded RNA poly(I:C) stimulation upregulates the TACI/TLR3/TRIF/TRAF6 expression and promotes IgA CSR and BAFF productions in tonsil mononuclear cells. TLR3 or BAFF siRNA decreases IgA expression. In IgAN rat models, TLR3/BAFF signaling was highly activated. With 200 μg poly(I:C) sodium salt into the left naris for 8 weeks, IgA was highly deposited on glomeruli. It also revealed that poly(I:C) activated TLR3/BAFF axis and IgA CSR in vivo. Conclusion: These data points toward the role of TLR3/BAFF axis in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with virus infection results in impaired mucosal and systemic IgA responses.

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Section: Animals and Experimental Designmentioning

confidence: 99%

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

He¹,

Peng²,

Wang³

et al. 2015

Am J Nephrol

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show abstract

“…Data from other studies also have shown that this method can build a stable animal model for IgAN [28][29][30] . IgAN was induced by continuous oral immunization with 0.1% BSA (G7516, Sigma Chemical Co., St. Louis, Mo., USA) with 6 m M HCl in tap water for 10 weeks, followed by tail intravenous injection of 1 mg BSA daily for 3 successive days.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Regulation of IgA Class Switch Recombination in Immunoglobulin A Nephropathy: Retinoic Acid Signaling and BATF

Peng²,

Chen³

et al. 2016

Am J Nephrol

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Background: Immunoglobulin (Ig) A nephropathy (IgAN) is the ﬁnding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Increasing evidence suggested that retinoic acid (RA) signaling selectively induces IgA isotype switching and basic leucine zipper transcription factor, ATF-like (BATF) controls the global regulators of class switch recombination (CSR) in lymphocytes. Great effort has been paid to identify whether impaired immune regulation along the ‘mucosa-bone marrow (BM) axis' play an important role in the pathogenesis of IgAN. Methods: The aim of the study was to investigate the expression of all-trans-RA (ATRA) and BATF, and to identify their impact on IgA CSR in IgAN patients and rat animal models. Blood samples and tonsillar tissue specimens were obtained from 22 patients with IgAN and 24 patients with chronic tonsillitis as control. Results: Immunohistochemical, RT-PCR and western blotting examination revealed that RA signaling and BATF productions are activated in IgAN patients compared with controls. Lipopolysaccharide and α-hemolytic streptococcus stimulation upregulated RA receptor (RAR) and BATF expression, promote IgA CSR and ATRA productions in tonsil mononuclear cells. RAR alpha (RARα) or BATF siRNA decreases IgA expression. We also built IgAN rat models and found that RARα, BATF and activation-induced cytidine deaminase were upregulated in the peripheral blood, spleen and BM. With ATRA (500 μg/kg body weight) treatment for 8 weeks, IgA deposition on glomeruli and mesangial cells proliferation increased. It also revealed that ATRA activated BATF and IgA CSR in vivo. Conclusion: These data point toward the role of RA signaling together with BATF in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with neoantigen results in impaired mucosal and systemic IgA responses.

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“…[21][22][23] For the control group, saline replaced the BGG. The IgAN model was established at the end of the 12th week.…”

Section: Establishment Of the Igan Modelmentioning

confidence: 99%

Rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms

Tian

Wang

et al. 2014

Exp Biol Med (Maywood)

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IgA nephropathy is the most frequent type of glomerulonephritis worldwide. The role of cell cycle regulation in the pathogenesis of IgA nephropathy has been studied. The present study was designed to explore whether rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms. After establishing an IgA nephropathy model, rats were randomly divided into four groups. Coomassie Brilliant Blue was used to measure the 24-h urinary protein levels. Renal function was determined using an autoanalyzer. Proliferation was assayed via Proliferating Cell Nuclear Antigen (PCNA) immunohistochemistry. Rat mesangial cells were cultured and divided into the six groups. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and flow cytometry were used to detect cell proliferation and the cell cycle phase. Western blotting was performed to determine cyclin E, cyclin-dependent kinase 2, p27Kip1 , p70S6K/p-p70S6K, and extracellular signal-regulated kinase 1/2/p-extracellular signal-regulated kinase 1/2 protein expression. A low dose of the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented an additional increase in proteinuria, protected kidney function, and reduced IgA deposition in a model of IgA nephropathy. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G1 phase. Rapamycin did not affect the expression of cyclin E and cyclindependent kinase 2. However, rapamycin upregulated p27 Kip1 at least in part via AKT (also known as protein kinase B)/mTOR. In conclusion, rapamycin can affect cell cycle regulation to inhibit mesangial cell proliferation, thereby reduce IgA deposition, and slow the progression of IgAN.

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Additive effect of PPAR-γ agonist and ARB in treatment of experimental IgA nephropathy

Cited by 25 publications

References 30 publications

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

Regulation of IgA Class Switch Recombination in Immunoglobulin A Nephropathy: Retinoic Acid Signaling and BATF

Rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms

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