RESUMEN
Heterozygous mutations in SNRPB, an essential core component of the five small ribonucleoprotein particles of the spliceosome, are responsible for cerebrocostomandibular syndrome (CCMS). We show that Snrpb heterozygous mouse embryos arrest shortly after implantation. Additionally, heterozygous deletion of Snrpb in the developing brain and neural crest cells models craniofacial malformations found in CCMS, and results in death shortly after birth. RNAseq analysis of mutant heads prior to morphological defects revealed increased exon skipping and intron retention in association with increased 5' splice site strength. We found increased exon skipping in negative regulators of the P53 pathway, along with increased levels of nuclear P53 and P53 target genes. However, removing Trp53 in Snrpb heterozygous mutant neural crest cells did not completely rescue craniofacial development. We also found a small but significant increase in exon skipping of several transcripts required for head and midface development, including Smad2 and Rere. Furthermore, mutant embryos exhibited ectopic or missing expression of Fgf8 and Shh, which are required to coordinate face and brain development. Thus, we propose that mis-splicing of transcripts that regulate P53 activity and craniofacial-specific genes contributes to craniofacial malformations. This article has an associated First Person interview with the first author of the paper.
Asunto(s)
Anomalías Craneofaciales , Micrognatismo , Animales , Anomalías Craneofaciales/genética , Humanos , Discapacidad Intelectual , Ratones , Micrognatismo/genética , Morfogénesis , Cresta Neural , Costillas/anomalías , Proteína p53 Supresora de Tumor/genética , Proteínas Nucleares snRNPRESUMEN
BACKGROUND: Interleukin-19 (IL-19) is a newly discovered cytokine belonging to the Interleukin-10(IL-10) family. IL-19 have indispensable functions in many inflammatory processes and also can induce the angiogenic potential of endothelial cells. The purpose of present study was to investigate the relation of serum interleukin-19 (IL-19) levels with diabetic nephropathy (DN). METHODS: Two hundred study groups of patients with type 2 diabetes mellitus (T2DM) (109 males and 91 females) were recruited, included normoalbuminuria(n = 102), microalbuminuria(n = 72) and macroalbuminuria(n = 26) . The 50 healthy blood donors were enrolled for the control group. All subjects were assessed for: IL-19, High-sensitivity C-reactive protein (Hs-CRP), Cystatin C, urinary albumin excretion rate (UAE) and glycosylated hemoglobin A1c(HbA1c). RESULTS: The serum IL-19 levels in DN patients were found to be significantly higher compared to controls. IL-19 levels were significantly positively correlated with Hs-CRP, Cystatin C, UAE and HbA1c(r = 0.623, 0.611,0.591 and 0.526 respectively, P < 0.01). Multivariable logistic regression analysis showed IL-19 levels (P = 0.01) were found to be independently associated with patients with DN. CONCLUSIONS: IL-19 is significantly positive correlated with UAE and Cystatin C. IL-19 may play an important role that contributes to the progression of diabetic nephropathy.
Asunto(s)
Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/diagnóstico , Interleucinas/sangre , Biomarcadores/sangre , China/epidemiología , Nefropatías Diabéticas/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
This study was to investigate the role of interleukin-19 (IL-19) and angiopoietin-2 (Ang-2) in angiogenesis of type 2 diabetes (T2DM). In 240 patients with T2DM, IL-19 and Ang-2 levels were higher, IL-19 was positively correlated with Ang-2. IL-19 and Ang-2 might be involved in angiogenesis of T2DM complications.