期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 306, 期 12, 页码 C1119-C1128出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00385.2013
关键词
HMGB1; PTEN; Akt; NF-kappa B; cell proliferation; mouse mesangial cell
资金
- National Natural Science Foundation [81000301, 81100517]
- 2012 Annual Program for New Century Excellent Talents [0300690202]
- Ministry of Education of China [20101323120007]
Our previous experiment confirmed that high-mobility group box chromosomal protein 1 (HMGB1) was involved in the pathogenesis of Lupus nephritis (LN) by upregulating the proliferation of the mouse mesangial cell line (MMC) through the cyclin D1/CDK4/p16 system, but the precise mechanism is still unknown. Therefore, in the present study, we demonstrated that HMGB1 induced the proliferation of MMC cells in a time-and concentration-dependent manner, downregulated phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression, increased the level of Akt serine 473 phosphorylation, and induced p65 subunit nuclear translocation. The overexpression of PTEN prevented the upregulation of HMGB1-induced proliferation by blocking the activation of Akt. The knockdown of Akt by siRNA technology and blocking the nuclear factor-kappa B (NF-kappa B) pathway using pyrrolidine dithiocarbamate (PDTC) and SN50, inhibitors of NF-kappa B, both attenuated the HMGB1-induced proliferation by counteracting the activation of the cyclin D1. In addition, while sh-Akt partly blocked the nuclear translocation of the p65 subunit, PDTC did not affect the activation of the Akt induced by HMGB1 in MMC cells. These findings indicate that HMGB1 induced the proliferation of MMC cells by activating the PTEN/phosphoinositide-3-kinase (PI3K)/Akt/NF-kappa B signaling pathway.
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