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PURPOSE@#Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro.@*METHODS@#Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD.@*RESULTS@#It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered.@*CONCLUSION@#Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.
Subject(s)
Animals , Rats , Claudins , Nerve Regeneration , Peripheral Nerve Injuries , Schwann Cells/pathology , Sciatic Nerve , Wallerian Degeneration/pathologyABSTRACT
Objective Nanobacteria are one of the factors for urinary calculi and its exact pathogenic mechanism is not yet clear.The aim of this study was to investigate the role of the CaSR -Claudin-14 regulatory channel in the formation of calculi . Methods Sixty Wistar male rats were equally randomized into a normal control group and nanobacterial group , the former injected via the tail vein with 1.2 mL of 0.9％ sodium chloride solution while the latter with 1.2 mL of nanobacterial suspension , both for once.Three of the rats in each group were sacrificed every week in the first 10 weeks after injection.Histopathological examination was performed every week to evaluate the stone formation in the kidneys of the rats , and the expressions of the CaSR and Claudin -14 proteins were determined by immunohistochemistry. Results From the 1st to the 10th week after injection, crystal particles were observed in the rat kidneys of the nanobacterial group, but not in the normal controls (52.4％ vs 0％, P<0.01).The expressions of CaSR and Claudin -14 showed no statistically significant differences between the nanobacterial and control groups in the first 3 weeks (P>0.05) but both gradually in-creased in the former group from the 4th to the 10th week as compared with the latter, mainly in membrane of the renal tubular epithelial cells. Conclusion The increased activity of the CaSR -Claudin-14 regulatory channel may play an important role in the formation of nanobacterial renal stone .
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Objective To investigate the alterations of tight junction proteins in duodenal mucosa from 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease(PD) model. Methods Rats were subjected with 6-OHDA in bilateral substantia nigra (SN) as PD model. The location and quantitative detecting techniques inclu-ding immunohisto- chemistry and western blotting were used to determine the expressions and alterations of tight junction proteins (claudin-1, occludin, ZO-1). Results Claudin-1, occludin and ZO-1 were highly expressed in the duodenal mucosa of PD models, where the expressions of occluding (P<0.001) and ZO-1 (P<0.001) were much lower, while the expression of claudin-1 had no alteration. Conclusions The down-regulated expres-sion of occludin and ZO-1 was detected in duodenal mucosa of PD models, which might be related to duodenal ulcer in PD.
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Objective To investigate the alterations of tight junction proteins in duodenal mucosa from 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease(PD) model. Methods Rats were subjected with 6-OHDA in bilateral substantia nigra (SN) as PD model. The location and quantitative detecting techniques inclu-ding immunohisto- chemistry and western blotting were used to determine the expressions and alterations of tight junction proteins (claudin-1, occludin, ZO-1). Results Claudin-1, occludin and ZO-1 were highly expressed in the duodenal mucosa of PD models, where the expressions of occluding (P<0.001) and ZO-1 (P<0.001) were much lower, while the expression of claudin-1 had no alteration. Conclusions The down-regulated expres-sion of occludin and ZO-1 was detected in duodenal mucosa of PD models, which might be related to duodenal ulcer in PD.
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Objective To investigate the expressions of calcium sensitive receptor (CaSR) and tight junction protein (Claudin)-14 in renal calcium oxalate stone rat model. Methods Thirty male SD rats were randomly divided into control group (n=15) and model group (n=15). The rat model of renal calcium oxalate stone was established by gavaging 1%glycol (2 mL/d) and 2% ammonium chloride. The expression of CaSR protein was detected using immunohistochemical assay. RT-PCR was used to detect the Claudin-14 mRNA expression. The expression levels of CaSR and Claudin-14 protein were de-tected by Western blot assay respectively. The full automatic biochemical analyzer was used to detect rat renal function and changes of blood and urine biochemical indices. Results A large stone crystallization was observed under light microscope in model group. The serum levels of Cr, BUN, 24-h urine calcium and urine volume were significantly higher in model group than those of control group (P<0.01). There were no significant differences in serum calcium level and urinary pH value be-tween two groups. The expression levels of Claudin-14 mRNA and CaSR protein were significantly higher in model group than those of control group (P<0.01). The Claudin-14 protein expression was specifically higher in renal tissues of model group. There was no Claudin-14 protein expression in control group. There was a positive correlation between CaSR and Claudin-14 protein expression in renal tissues of model group. Also, CaSR and Claudin-14 protein expressions were posi-tively correlated with the 24-h urine volume. Conclusion The increased expressions of CaSR and Claudin-14 involved in the formation of kidney stone by increasing the urinary calcium excretion.
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Objective The calcium oxalate stone is the most common type of the kidney stones.By building the rat renal calcium oxalate stone model, preliminary study the function of CaSR-Claudin14 regulating pathways on renal calcium oxalate stone for-mation model in rats. Methods 30 Male S-D rats were randomly divided into control group (n=15) and model group (n=15). Adult male S-D rats were given ethylene glycol and ammonium chloride to induce urolithiasis.Application of full automatic biochemical analyzer to test rat renal function and the changes of urine biochemical index.Immunohistochemistry was used to detect the expression of CaSR protein;RT-PCR was used to detect the Claudin-14 mRNA expression;Western Blotting was used to detect the expression of CaSR and Claudin-14 protein respectively. Results By observing model group has large stones crystallization under light microsco-py;model group rats 24 h urine calcium are significantly higher than control group([9.66 ±1.10]mmol vs [3.26 ±0.60]mmol, P0.05 ) .Expression of Claudin-14 mRNA in the model group is significantly higher than normal control group([0.150 ± 0.004] vs [0.047 ±0.008], P<0.01); Expression of Claudin-14 protein in the model group is significantly higher than normal control group([1.526 ±0.089] vs 0, P<0.01).Expression of CaSR protein in the model group is significantly higher than normal control group([6.697 ±0.051] vs [5.016 ±0.053], P<0.05). Conclusion CaSR can raise the expression of Claudin-14, increase re-nal tubular urinary calcium excretion to promote renal calcium oxalate stone formation.