Ufl1 deficiency causes kidney atrophy associated with disruption of endoplasmic reticulum homeostasis

The UFMylation modification is a novel ubiquitin-like conjugation system,consisting of UBA5(E1),UFC1(E2),UFL1(E3),and the conjugating molecule UFM1.Deficiency in this modification leads to embryonic lethality in mice and diseases in humans.However,the function of UFL1 is poorly characterized.Studies on Ufl1 conditional knockout mice have demonstrated that the deletion of Ufl1 in cardiomyocytes and in intestinal epithelial cells causes heart failure and increases susceptibility to experimentally induced colitis,respectively,suggesting an essential role of UFL1 in the maintenance of the homeostasis in these organs.Yet,its physiological function in other tissues and organs remains completely unknown.In this study,we generate the nephron tubules specific Ufl1 knockout mice and find that the absence of Ufl1 in renal tubular results in kidney atrophy and interstitial fibrosis.In addition,Ufl1 deficiency causes the activation of unfolded protein response and cell apoptosis,which may be responsible for the kidney atrophy and interstitial fibrosis.Collectively,our results have demonstrated the crucial role of UFL1 in regulating kidney function and maintenance of endoplasmic reticulum homeostasis,providing another layer of understanding kidney atrophy.

Antioxidant Machinery Related to Decreased MDA Generation by Thymus Algeriensis Essential Oil-induced Liver and Kidney Regeneration

Objective This study was conducted to determine the histopathological and biochemical effects of Thymus algeriensis essential oil （TEO） on hydrogen peroxide （H2O2）-induced oxidative stress in liver and kidney tissues of rats. Methods Rats were treated in six groups and were exposed for 2 weeks to low （LD; 100 μmol/L） and high doses （HD; 1 mmol/L） of H2O2 in the presence or absence of TEO （180 mg/kg）. Liver and kidney atrophy was measured by using biochemical and histopathological assays. Results Our study demonstrated that H2O2 induced liver and kidney atrophy, as evidenced by the significant elevation of serum aminotransferase, urea, and creatinine levels compared with those in the control rats. Urea levels were estimated by evaluating the activity of serum urease that hydrolyzes urea into CO2 and ammonia. However, TEO treatment significantly alleviated oxidative stress in the H2O2-induced liver and kidney toxicity model by reducing the levels of malondialdehyde concomitantly with marked elevations in superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase, as well as decrease in glutathione activity. Conclusion Our data demonstrated that TEO protected against H202 toxicity by decreasing oxidant levels and DNA damage, as well as increasing antioxidant levels, indicating that TEO has a spectrum of antioxidant and DNA-protective properties.