Project description:Receptor-interacting protein kinase 1 (RIP1)-mediated necroptosis plays a vital role in various diseases, but the involvement of RIP1 and its functional mechanism in osteoarthritis pathogenesis remains largely unknown. To identify molecular targets of RIP1 in chondrocytes, RNA sequencing was performed in chondrocytes treated with adenovirus expressing RIP1 or vector control. We found that 9857 genes were differentially expressed in chondrocytes after RIP1 overexpression. GO analysis indicated that DNA replication, chromosome segregation and regulation of cell cycle process were upregulated, while terms including cartilage development, skeletal system development, extracellular matrix organization, skeletal system morphogenesis, chondrocyte differentiation, collagen fibril organization and limb development were downregulated. Pathway analysis revealed that IL-17 signaling pathway, cell cycle, DNA replication, proteasome, TNF signaling pathway, cellular senescence and p53 signaling pathway were significantly upregulated by RIP1, meanwhile, ECM-receptor interaction, other glycan degradation and glycosaminoglycan degradation were downregulated. These results underscore the importance of RIP1 in OA by perturbing a series of essential events during disease progression such like cell cycle regulation, chondrocyte differentiation, inflammation and ECM remodeling.
Project description:Investigation of whole genome gene expression level changes in a Vibrio cholerae O395N1 delta-nqrA-F mutant, compared to the wild-type strain.
Project description:Mycobacterium tuberculosis is exposed to a variety of stresses during a chronic infection, as the immune system simultaneously produces bactericidal compounds and starves the pathogen for essential nutrients. The intramembrane protease, Rip1, plays an important role in the adaptation to these stresses, at least partially by the cleavage of membrane bound transcriptional regulators. Although Rip1 is known to be critical for surviving copper intoxication and nitric oxide exposure, these stresses do not fully account the regulatory protein’s essentiality during infection. In this work, we demonstrate that Rip1 is also necessary for growth in low iron and zinc conditions, similar to those imposed by the immune system. Using a newly generated library of sigma factor mutants, we show that the known regulatory target of Rip1, SigL, shares this defect. Transcriptional profiling under iron limiting conditions supported the coordinated activity of Rip1 and SigL and demonstrated that the loss of these proteins produces an exaggerated iron starvation response. These observations demonstrate that Rip1 coordinates several aspects of metal homeostasis and suggest that a Rip1- and SigL-dependent pathway is involved in the adaptation to the iron deficient environments encountered during infection.
