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

Chen X, Peng S, Zeng H, Fu A, Zhu Q - Indian J Pharmacol (2015 Jan-Feb)

Bottom Line: 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 mechanism may involve inhibition of renal TLR4 and TGF-β1 secretion.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China.

ABSTRACT

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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(a) Transforming growth factor-β1 immunohistochemical staining of kidney sections (b) Toll-like receptor 4 immunohistochemical staining of kidney sections (c) Toll-like receptor 9 immunohistochemical staining of kidney sections
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Figure 2: (a) Transforming growth factor-β1 immunohistochemical staining of kidney sections (b) Toll-like receptor 4 immunohistochemical staining of kidney sections (c) Toll-like receptor 9 immunohistochemical staining of kidney sections

Mentions: Immunohistochemical assay with paraffin-embedded kidney sections was used to detect TLR4, TLR9, and TGF-β1 protein expression in the renal cortex. Immunohistochemical stain showed that TGF-β1 protein was obviously detected in the cytoplasm of most tubular epithelial cells and tubulointerstitial of all biopsies, and slightly detected in the glomeruli of some biopsies from IgAN rats. However, the control group sections stain showed that TGF-β1 protein was slightly expressed within the cytoplasm of a few renal tubular cells with scattered and sparse patterns and not detected in the glomeruli. The quantitative value of integrated optical density of IgAN rats was much higher than that of the control group (P < 0.05). Compared with the IgAN rats, there was an obvious decrease in TGF-β1 protein expression within the cytoplasm of some renal tubular cells of rhein-prevented and rhein-treated rats. The quantitative values of integrated optical density of TGF-β1 protein were not statistically significant between the rhein-prevented or rhein-treated rats and control rats (P > 0.05) [Figure 2a, Table 3]. TLR4 protein was found in the cytoplasma of most renal tubular cells and glomeruli. The quantitative values of integrated optical density demonstrated that renal tubular and glomerular TLR4 protein expression of IgAN rats was significantly up-regulated in comparison to control rats. With rhein-prevented and rhein-treated, TLR4 protein expression became weaker than IgAN rats, and there was no significant difference compared with controls [Figure 2b, Table 3]. TLR9 protein weakly existed in the cytoplasma of some renal tubular cells and glomeruli from all the four group rats. The quantitative value of integrated optical density between the four groups was not statistically significant [Figure 2c, Table 3].


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

Chen X, Peng S, Zeng H, Fu A, Zhu Q - Indian J Pharmacol (2015 Jan-Feb)

(a) Transforming growth factor-β1 immunohistochemical staining of kidney sections (b) Toll-like receptor 4 immunohistochemical staining of kidney sections (c) Toll-like receptor 9 immunohistochemical staining of kidney sections
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4375814&req=5

Figure 2: (a) Transforming growth factor-β1 immunohistochemical staining of kidney sections (b) Toll-like receptor 4 immunohistochemical staining of kidney sections (c) Toll-like receptor 9 immunohistochemical staining of kidney sections
Mentions: Immunohistochemical assay with paraffin-embedded kidney sections was used to detect TLR4, TLR9, and TGF-β1 protein expression in the renal cortex. Immunohistochemical stain showed that TGF-β1 protein was obviously detected in the cytoplasm of most tubular epithelial cells and tubulointerstitial of all biopsies, and slightly detected in the glomeruli of some biopsies from IgAN rats. However, the control group sections stain showed that TGF-β1 protein was slightly expressed within the cytoplasm of a few renal tubular cells with scattered and sparse patterns and not detected in the glomeruli. The quantitative value of integrated optical density of IgAN rats was much higher than that of the control group (P < 0.05). Compared with the IgAN rats, there was an obvious decrease in TGF-β1 protein expression within the cytoplasm of some renal tubular cells of rhein-prevented and rhein-treated rats. The quantitative values of integrated optical density of TGF-β1 protein were not statistically significant between the rhein-prevented or rhein-treated rats and control rats (P > 0.05) [Figure 2a, Table 3]. TLR4 protein was found in the cytoplasma of most renal tubular cells and glomeruli. The quantitative values of integrated optical density demonstrated that renal tubular and glomerular TLR4 protein expression of IgAN rats was significantly up-regulated in comparison to control rats. With rhein-prevented and rhein-treated, TLR4 protein expression became weaker than IgAN rats, and there was no significant difference compared with controls [Figure 2b, Table 3]. TLR9 protein weakly existed in the cytoplasma of some renal tubular cells and glomeruli from all the four group rats. The quantitative value of integrated optical density between the four groups was not statistically significant [Figure 2c, Table 3].

Bottom Line: 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 mechanism may involve inhibition of renal TLR4 and TGF-β1 secretion.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus