The neurofibromatosis 1 (NF1) gene encodes a protein neurofibromin, which contains a glutamyl transpeptidase (GTP)-activating protein (GAP)-related domain: NF1 GRD. This domain is able to down-regulate P21ras by stimulating its intrinsic GTPase. Because P2lras has an important role in regulating growth and differentiation, somatic mutations in the NF1 gene may result in mutant neurofibromins that might interfere with the Ras signaling pathway and contribute to the development of tumors. In this study, we used polymerase chain reaction (PCR)-coupled single-stranded conformational polymorphism (SSCP) and DNA sequencing to examine possible mutations in the NF1 GRD in human pituitary tumors. We screened 36 nonfunctioning and 20 growth hormone—secreting adenomas. No mutation was detected in these tumors. Our results indicate that inactivation of neurofibromin may not have a primary role in the formation of pituitary adenomas. 相似文献
Background: Despite years of research, the treatment of acute kidney injury (AKI) remains a significant challenge. Animal studies presented causal links between elevated regulatory T cell (Treg) response and better prognosis in AKI. Previous studies in mice and humans showed that TIM-3+ Treg cells were more potent than TIM-3- Treg cells. In this study, we investigated the role of TIM-3 in Treg in AKI patients.
Methods: Peripheral blood from AKI patients and healthy controls were gathered, and TIM-3+ Treg subset was examined.
Results: Compared to healthy controls, the AKI patients presented a significant upregulation in the frequency of circulating CD4+CD25+ T cells; however, the majority of this increase was from the CD4+CD25+TIM-3- subset, and the frequency of CD4+CD25+TIM-3+ T cells was downregulated in AKI patients. In both healthy controls and AKI patients, the CD4+CD25+TIM-3+ T cells expressed higher levels of Foxp3, and were more potent at expressing LFA-1, LAG-3, CTLA-4, IL-10 and TGF-β. In addition, the CD4+CD25+TIM-3+ T cells from both healthy controls and AKI patients presented higher capacity to suppress CD4+CD25- T cell proliferation than the CD4+CD25+TIM-3- T cells. Interestingly, the total CD4+CD25+ T cells from AKI patients presented significantly lower inhibitory capacity than those from healthy controls, indicating that the low frequency of CD4+CD25+TIM-3+ T cells was restricting the efficacy of the Treg responses in AKI patients.
Conclusions: We demonstrated that TIM-3 downregulation impaired the function of Treg cells in AKI. The therapeutic potential of CD4+CD25+TIM-3+ T cells in AKI should be investigated in future studies. 相似文献