Unknown,Transcriptomics,Genomics,Proteomics

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Regulatory function of Pja2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells

ABSTRACT: Praja2 (Pja2), a member of the growing family of mammalian RING E3 ubiquitin ligases, is reportedly involved not only in several types of cancer but also in neurological diseases and disorders. However, the underlying genetic mechanism of Pja2 regulation in the nervous system remains unclear. To study the cellular and molecular function of Pja2 in mouse hippocampal neuronal cells (MHNCs), we used gain- and loss-of-function manipulations of Pja2 in HT-22 cells and tested their regulatory effects on three Alzheimer's disease (AD) genes and cell proliferation. We found that the expression of AD markers including App, Mapt and Gsap could be inhibited by Pja2 overexpression and activated by Pja2 knockdown. In addition, HT-22 cell proliferation was enhanced by Pja2 upregulation and suppressed by its downregulation. We also applied RNA-Seq to evaluate and quantify the targets that responded to the enforced expression of Pja2. In particular, P2rx3 and P2rx7, which have different expression patterns in the critical calcium signaling pathway, were shown to mediate the regulatory effect of Pja2 in HT-22 cells. Functional studies indicated that Pja2 regulated HT-22 cell development and AD marker genes by inhibiting P2rx3 but promoting P2rx7, a gene downstream of P2rx3. In conclusion, our results provide new insights into the regulatory function of the gene Pja2 in MHNCs, underscoring the potential relevance of this molecule to the pathophysiology of AD.

INSTRUMENT(S): Illumina HiSeq 3000

ORGANISM(S): Mus musculus

SUBMITTER: mengtinggong gong

PROVIDER: E-MTAB-6464 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Regulatory function of Pja2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells

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