Interleukin-22 ameliorated acetaminophen-induced kidney injury by inhibiting mitochondrial dysfunction and inflammatory responses.

Acetaminophen (APAP) overdose can lead to acute, severe kidney injury, which has recently attracted considerable attention among researchers and clinicians. Unfortunately, there are no well-established treatments for APAP-induced renal injury, and the molecular mechanism of APAP-induced kidney injury is still unclear. Herein, we explored the protective effects of interleukin (IL)-22 on APAP-induced renal injury and the underlying molecular basis. We found that IL-22 could significantly alleviate the accumulation of reactive oxygen species (ROS) and ameliorate mitochondrial dysfunction, reducing APAP-induced renal tubular epithelial cell (TEC) death in vitro and in vivo. Furthermore, IL-22 could downregulate the APAP-induced NLRP3 inflammasome activation and mature IL-1ß release in kidney injury. Additionally, the APAP-mediated upregulation of the serum levels of IL-18, TNF-α, IL-6, and IL-1ß was obviously decreased, suggesting IL-22 has inhibitory effects on inflammatory responses. Conclusively, our study demonstrated that IL-22 exerted ameliorative effects on APAP-induced kidney injury by alleviating mitochondrial dysfunction and NLRP3 inflammasome activation, suggesting that IL-22 represents a potential therapeutic approach to treat APAP-induced kidney injury. KEY POINTS: • IL-22 could ameliorate APAP that triggered oxidative stress and mitochondrial dysfunction. • IL-22 could reduce APAP that caused inflammatory responses. Graphical abstract.

[The effect of cyclin kinase inhibitor p27 on tumor necrosis factor-alpha induced mesangial cell proliferation].

OBJECTIVE: To investigate the role of cyclin kinase inhibitor p27 on proliferation of mesangial cell (MC) induced by tumor necrosis factor-alpha (TNF-alpha). METHODS: p27 protein of MC lysate was detected with Western blotting analysis. The degree of MC proliferation was estimated through [(3)H] thymidine incorporation. The effect of reducing p27 expression on MC proliferation was analysed with p27 antisense oligodeoxynucleotide (ODN) phosphorothioate. RESULTS: TNFalpha (200 000 U/L) decreased p27 level to 0.6 +/- 0.1 from 1.1 +/- 0.1 of MC lysate cultured in serum-free DMEM for 24 hours (P < 0.01) and increased [(3)H] thymidine incorporation to 2 060 +/- 112 from 685 +/- 53 cpm/well (P < 0.01). p27 antisense ODN transfection decreased p27 level of MC stimulated by TNF-alpha for 24 hours (0.3 +/- 0.1 vs 0.6 +/- 0.1, P < 0.01) and increased [(3)H] thymidine incorporation (2 420 +/- 130 vs 2 060 +/- 112 cpm/well, P < 0.05) in 24 hours of culture. CONCLUSION: The decline of p27 protein may play an important role in MC proliferation induced by TNF-alpha. Because the cell cycle is controlled by the interplay between the positive cell cycle regulatory proteins (CCRP) and negative CCRP, further research is needed to study the expression of the positive and negative CCRP in MC in order to understand better the role of CCRP in MC proliferation.

WS1 gene mutation analysis of Wolfram syndrome in a Chinese patient and a systematic review of literatures.

Wolfram syndrome is a rare hereditary disease characterized by diabetes mellitus and optic atrophy. The outcome of this disease is always poor. WFS1 gene mutation is the main cause of this disease. A patient with diabetes mellitus, diabetes insipidus, renal tract disorder, psychiatric abnormality, and cataract was diagnosed with Wolfram syndrome. Mutations in open reading frame (ORF) of WFS1 gene was analyzed by sequencing. Mutations in WFS1 gene was also summarized by a systematic review in Pubmed and Chinese biological and medical database. Sequencing of WFS1 gene in this patient showed a new mutation, 1962G>A, and two other non-sense mutations, 2433A>G and 2565G>A. Systematic review included 219 patients in total and identified 172 WFS1 gene mutations, most of which were located in Exon 8. These mutations in WFS1 gene might be useful in prenatal diagnosis of Wolfram syndrome.