Protection of rhein on IgA nephropathy mediated by inhibition of fibronectin expression in rats

Peng, Sheng-Nan; Zeng, Huihong; Fu, Aixiang; Chen, Xiaowen; Zhu, Qing

doi:10.4103/0253-7613.108309

Cited by 14 publications

(7 citation statements)

References 20 publications

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“…However, aside of αSMA as main marker of mature myofibroblasts, hypoxia affected representative pro-fibrotic genes including cytokines, proteoglycans, integrins, MMPs and their inhibitors TIMPs, indicating increased myofibroblast activity 23 . The key finding that Rhein substantially reduced αSMA protein abundance in HCF-v and oppositely regulated other pro-fibrotic genes was in line with several observations reported in other tissues [24][25][26] .…”

Section: Discussionsupporting

confidence: 89%

Rhein, a novel Histone Deacetylase (HDAC) inhibitor with antifibrotic potency in human myocardial fibrosis

Barbosa

Fahlbusch

Wiza

et al. 2020

Sci Rep

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Although fibrosis depicts a reparative mechanism, maladaptation of the heart due to excessive production of extracellular matrix accelerates cardiac dysfunction. The anthraquinone Rhein was examined for its anti-fibrotic potency to mitigate cardiac fibroblast-to-myofibroblast transition (FMT). Primary human ventricular cardiac fibroblasts were subjected to hypoxia and characterized with proteomics, transcriptomics and cell functional techniques. Knowledge based analyses of the omics data revealed a modulation of fibrosis-associated pathways and cell cycle due to Rhein administration during hypoxia, whereas p53 and p21 were identified as upstream regulators involved in the manifestation of cardiac fibroblast phenotypes. Mechanistically, Rhein acts inhibitory on HDAC classes I/II as enzymatic inhibitor. Rhein-mediated cellular effects were linked to the histone deacetylase (HDAC)-dependent protein stabilization of p53 under normoxic but not hypoxic conditions. Functionally, Rhein inhibited collagen contraction, indicating anti-fibrotic property in cardiac remodeling. This was accompanied by increased abundance of SMAD7, but not SMAD2/3, and consistently SMAD-specific E3 ubiquitin ligase SMURF2. In conclusion, this study identifies Rhein as a novel potent direct HDAC inhibitor that may contribute to the treatment of cardiac fibrosis as antifibrotic agent. As readily available drug with approved safety, Rhein constitutes a promising potential therapeutic approach in the supplemental and protective intervention of cardiac fibrosis.

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Section: Discussionsupporting

confidence: 89%

Rhein, a novel Histone Deacetylase (HDAC) inhibitor with antifibrotic potency in human myocardial fibrosis

Barbosa

Fahlbusch

Wiza

et al. 2020

Sci Rep

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“…Direct immunofluorescence staining was performed as described previously. [ 8 ] In brief: Frozen kidney sections fixed with cold acetone for 10 min at 4°C were treated with 10% normal sheep serum in phosphate buffer sodium (PBS) to block nonspecific reaction and then incubated with the FITC-conjugated mouse against rat IgA antibodies (1:100) overnight at 4°C. Stained kidney sections were viewed under fluorescence microscope, and the description of results is represented in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

“…This assay was performed as described previously. [ 8 ] Briefly, paraffin-embedded kidney sections were processed in sodium citrate buffer (0.01 mol/L, potential of hydrogen 6) for 15 min at maximum power in the microwave. The sections were incubated with 3% H 2 O 2 deionized water at room temperature for 10 min and treated with 10% normal goat serum at room temperature for 20 min to block endogenous peroxidase and nonspecific reaction.…”

Section: Methodsmentioning

confidence: 99%

“…[ 5 6 7 ] In previous study, it is demonstrated that rhein prevents the development of glomerulosclerosis and halts the progression of IgAN via inhibition of fibronectin (FN) and α-smooth muscle actin (α-SMA) expression. [ 8 ] It is well-known that toll-like receptors (TLRs) have been reported to be involved in the pathogenesis of IgAN. [ 9 10 ] TLR4 promotes mesangial cell injury and renal fibrosis by induction of pro-inflammatory cytokines, profibrotic molecule, and transforming growth factor-β1 (TGF-β1) signaling in Chronic Kidney Disease.…”

Section: Introductionmentioning

confidence: 99%

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Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy

et al. 2015

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Objectives:The objective was to investigate the protective effects of rhein on renal histology change and the effects of rhein on renal tissue toll-like receptor (TLR) 4, TLR9, transforming growth factor-β1 (TGF-β1) expression in immunoglobulin A nephropathy (IgAN) rats.Materials and Methods:Bovine serum albumin-lipopolysaccharide-carbon tetrachloride 4 method was used to establish IgAN model. Thirty-two male sprague dawley rats were randomly divided into the control group, IgAN model group, rhein-prevented group, and rhein-treated group. 24-h urinary protein (UP), creatinine, urea, alanine aminotransferase (ALT), total protein (TP) contents in the serum of rats were detected with automatic biochemical analyzer and renal pathological changes were observed by the hematoxylin and eosin and periodic acid-Schiff staining. The glomerular deposition of IgA was measured by immunofluorescence staining. Real-time polymerase chain reaction and immunohistochemistry were used to detect renal tissue contents of TLR4, TLR9, TGF-β1 messenger ribonucleic acid and protein expression.Results:The biochemical parameters results of IgAN model rats showed that the 24-h UP excretion and ALT concentration were much higher, and TP concentration was much lower than those of the control group (P < 0.05). Granule-like or mass-like IgA depositions in the mesangial area, glomerular hypercellularity, hyperplasia of mesangial matrix, and tubulointerstitial fibrosis were found in IgAN group. Rhein-prevented and rhein-treated both improved the biochemical parameters and relieved renal pathological injury. The expressions of renal tissue TLR4, TGF-β1, but not TLR9 were significantly elevated in IgAN model rats (P < 0.05). Rhein-prevented and rhein-treated both inhibited TLR4 and TGF-β1 expressions.Conclusion:Rhein significantly improved the serum and urine biochemical parameters, and attenuated the glomerular pathological changes and tubulointerstitial fibrosis in IgAN rats. The mechanism may involve inhibition of renal TLR4 and TGF-β1 secretion.

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“…Rhein markedly ameliorated the glomerular hypertrophy, mesangial expansion, excessive extracellular matrix, and renal capsule dilation in IgAN rats. Additionally, rhein administration evidently decreased IgA deposition in glomerulus, the volume of urinary red blood cells, 24-h urinary protein excretion, and the expression of upregulated FN and α -SMA in renal tissue [ 17 ]. In chronic allograft nephropathy rat models, rhein improved renal function through reductions of renal fibrosis and interstitial inflammation and increases of bone morphogenetic protein 7 and hepatic growth factor levels.…”

Section: Pharmacologymentioning

confidence: 99%

Rhein: A Review of Pharmacological Activities

Zhou

Xia

Yue

et al. 2015

Evidence-Based Complementary and Alternative Medicine

150

114

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Rhein (4, 5-dihydroxyanthraquinone-2-carboxylic acid) is a lipophilic anthraquinone extensively found in medicinal herbs, such as Rheum palmatum L., Cassia tora L., Polygonum multiflorum Thunb., and Aloe barbadensis Miller, which have been used medicinally in China for more than 1,000 years. Its biological activities related to human health are being explored actively. Emerging evidence suggests that rhein has many pharmacological effects, including hepatoprotective, nephroprotective, anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. The present review provides a comprehensive summary and analysis of the pharmacological properties of rhein, supporting the potential uses of rhein as a medicinal agent.

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Protection of rhein on IgA nephropathy mediated by inhibition of fibronectin expression in rats

Cited by 14 publications

References 20 publications

Rhein, a novel Histone Deacetylase (HDAC) inhibitor with antifibrotic potency in human myocardial fibrosis

Rhein, a novel Histone Deacetylase (HDAC) inhibitor with antifibrotic potency in human myocardial fibrosis

Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy

Rhein: A Review of Pharmacological Activities

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