ABSTRACT
Ring-finger protein 5 (RNF5) is an E3 ubiquitin ligase which is expressed in a variety of human tissues. RNF5 is involved in the regulation of endoplasmic reticulum stress, inflammation, and innate immunity and plays an important role in the occurrence and development of various tumors. However, the role of RNF5 in cardiac hypertrophy has not been reported. In this study, we found the expression of RNF5 was increased in the hearts of mice with pathological cardiac hypertrophy. The loss-of-function research demonstrated that RNF5 deficiency exacerbated cardiac hypertrophy, whereas gain-of-function studies revealed that overexpression of RNF5 had opposite effects. The stimulator of interferon genes (STING) is a signaling molecule that can activate type I interferon immunity, which can meditate inflammation and immune response in many diseases. The protein-protein interaction experiments confirmed that STING interacted with RNF5. Further studies showed that RNF5 inhibited cardiac hypertrophy by promoting STING degradation through K48-linked polyubiquitination. Therefore, we defined RNF5 as importantly regulated signaling for cardiac hypertrophy.
Subject(s)
Interferon Type I , Ubiquitin-Protein Ligases , Animals , Humans , Mice , Cardiomegaly/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Inflammation , Interferon Type I/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , UbiquitinationABSTRACT
OBJECTIVE: To investigate the incidence and correlative factors of metabolic syndrome (MS) in patients with systemic lupus erythematosus (SLE). METHODS: A total of 116 SLE patients and 115 controls were enrolled into the study. The incidence of MS, SLE disease activity index (SLEDAI) of patients with SLE combined with MS (MS-SLE) and patients without MS (n-MS-SLE), lupus characteristics, cumulative glucocorticoids, administration dose of glucocorticoids and hydroxychloroquine were compared between SLE group and the control group. RESULTS: The incidence of MS of SLE group was obviously higher than that of the control (34.48% vs 14.78%, P < 0.05). The ratios of patients with lower HDL-C, higher TG and higher blood pressure in SLE group (50.86%, 56.03%, 46.55%) were higher than those in the controls (34.78%, 16.52%, 20.00%, all P < 0.05). MS-SLE group had significantly higher mean waist circumference, BMI, systolic blood pressure and diastolic blood pressure and lower HDL-C than n-MS-SLE group (all P < 0.05). No significant difference was found regarding duration of disease, renal involvement, ESR, C-reactive protein,high-sensitivity C-reactive protein, SLEDAI, cumulative and current glucocorticoids use in MS-SLE group and n-MS-SLE group. The ratio of patients taking hydroxychloroquine in n-MS-SLE group was higher than that of MS-SLE group (46.05% vs 15.00%, P < 0.05). CONCLUSIONS: Patients with SLE has a higher incidence rate of MS. Hydroxychloroquine may reduce their MS incidence.
Subject(s)
Glucocorticoids/therapeutic use , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Metabolic Syndrome/etiology , Adolescent , Adult , Case-Control Studies , Female , Humans , Hydroxychloroquine/therapeutic use , Incidence , Male , Middle Aged , Young AdultABSTRACT
OBJECTIVE: To compare the difference of polycyclic aromatic hydrocarbons (PAHs) levels in the urban air and the scores of Neonatal Behavioral Neurological Assessment (NBNA) between Taiyuan and Changzhi cities and to explore the effects of PAHs in the urban air during pregnancy on neonatal behavioral neurological development. METHODS: High-performance liquid chromatography (HPLC) with subsequent fluorescence detection was used to determine the PAHs levels in the cooperational hospitals in Changzhi and Taiyuan cities and the urinary 1-hydroxypyrene levels of the 297 pregnant women living Changzhi and Taiyuan cities during Nov. 2009 to May 2010. NBNA was used to determine the development of neonatal neural behavior. The differences of PAHs levels in the urban air, the pregnant women urinary 1-hydroxypyrene levels and NBNA scores between Taiyuan and Changzhi were compared. RESULTS: There are significant differences of levels of pyrene, benz [a] anthracene, Chrysene, benz [a] pyrene, dibenz [a, h] anthracene in the urban air between Taiyuan and Changzhi (P < 0.10). The median of urinary 1-hydroxypyrene levels in pregnant women of Taiyuan was 1.140 microg/mmolCr, (P25 was 0.457 microg/mmolCr, P75 was 2.678 microg/mmolCr), the median of urinary 1-hydroxypyrene levels in pregnant women of Changzhi was 0.761 microg/mmolCr, (P25 was 0.133 microg/mmolCr, P75 was 2.095 microg/mmolCr). There are significant differences of urinary 1-hydroxypyrene levels in pregnant women between Taiyuan and Changzhi (t = -3.140, P = 0.002). There are significant differences of the NBNA scores, capacity scores, passive muscle tension scores, active muscle tension scores and general assessment scores between Taiyuan and Changzhi (P < 0.10). There was correlation between NBNA scores and urinary 1-hydroxypyrene level in pregnant women. CONCLUSION: The PAHs in the urban air during pregnancy may adversely affect the neonatal neurobehavioral development.
