New discovery rarely runs smooth: an update on progranulin/TNFR interactions

Progranulin (PGRN) is a growth factor implicated in various pathophysiological processes, including wound healing, inflammation, tumorigenesis, and neurodegeneration. It was previously reported that PGRN binds to tumor necrosis factor receptors (TNFR) and has therapeutic effects in inflammatory arthritis (Tang et. al, in Science 332:478-484, 2011); however, Chen et al. reported their inability to demonstrate the PGRN-TNFR interactions under their own conditions (Chen et. al, in J Neurosci 33:9202-9213, 2013). A letter-to-editor was then published by the original group in response to the Chen et al. paper that discussed the reasons for the latter's inability to recapitulate the interactions. In addition, the group published follow-up studies that further reinforced and dissected the interactions of PGRN-TNFR. Recently, the dispute about the legitimacy of PGRN-TNFR interactions appears to be finally settled with independent confirmations of these interactions in various conditions by numerous laboratories. This review presents a chronological update on the story of PGRN-TNFR interactions, highlighting the independent confirmations of these interactions in various diseases and conditions.

Identification of 5-flank upstream regulation region of CD226 / 中国免疫学杂志

Objective:To identify the function of the 5′-flank upstream regulation region of human CD226 gene.Methods:The upstream regulation region of CD226 was cloned by PCR and ligated into pGL3 vector. Then the vector was transfected into Jurkat cell and luciferase activity was detected after 48 h culture.Results:CD226 gene may have two promoters, P1 and P2,which were located at the region of -843--319 bp and +1-+181 bp respectively, and PMA can up-regulate P1 while down-regulate P2. Both P1 and P2 can be up-regulated by A23187, especially P2.Conclusion:CD226 gene may have two promoters, and PMA and A23187 can regulate CD226 promoter activity in the similar pattern of protein level.