PMID- 24760979 OWN - NLM STAT- MEDLINE DCOM- 20140818 LR - 20220408 IS - 1522-1563 (Electronic) IS - 0363-6143 (Linking) VI - 306 IP - 12 DP - 2014 Jun 15 TI - The PTEN/PI3K/Akt signaling pathway mediates HMGB1-induced cell proliferation by regulating the NF-kappaB/cyclin D1 pathway in mouse mesangial cells. PG - C1119-28 LID - 10.1152/ajpcell.00385.2013 [doi] AB - 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-kappaB (NF-kappaB) pathway using pyrrolidine dithiocarbamate (PDTC) and SN50, inhibitors of NF-kappaB, 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-kappaB signaling pathway. CI - Copyright (c) 2014 the American Physiological Society. FAU - Feng, Xiao-Juan AU - Feng XJ AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and. FAU - Liu, Shu-Xia AU - Liu SX AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and. FAU - Wu, Chao AU - Wu C AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and. FAU - Kang, Peng-Peng AU - Kang PP AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and. FAU - Liu, Qing-Juan AU - Liu QJ AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and. FAU - Hao, Jun AU - Hao J AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and. FAU - Li, Hong-Bo AU - Li HB AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and. FAU - Li, Fan AU - Li F AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and. FAU - Zhang, Yu-Jun AU - Zhang YJ AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and. FAU - Fu, Xiao-Hui AU - Fu XH AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and. FAU - Zhang, San-Bing AU - Zhang SB AD - Department of Hand and Foot Surgery, Third Hospital of Shijiazhuang City, Shijiazhuang, China. FAU - Zuo, Lian-Fu AU - Zuo LF AD - Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and zlf9205@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140423 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, mouse) RN - 0 (NF-kappa B) RN - 136601-57-5 (Cyclin D1) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (Pten protein, mouse) SB - IM MH - Animals MH - Cell Proliferation MH - Cyclin D1/*genetics/metabolism MH - Gene Knockdown Techniques MH - HMGB1 Protein/*genetics/metabolism MH - Lupus Nephritis/*genetics/metabolism/pathology MH - Mesangial Cells/*metabolism MH - Mice MH - NF-kappa B/genetics/metabolism MH - Oncogene Protein v-akt/genetics/metabolism MH - PTEN Phosphohydrolase/*genetics/metabolism MH - Phosphatidylinositol 3-Kinases/genetics MH - Phosphorylation MH - Signal Transduction/genetics OTO - NOTNLM OT - Akt OT - HMGB1 OT - NF-kappaB OT - PTEN OT - cell proliferation OT - mouse mesangial cell EDAT- 2014/04/25 06:00 MHDA- 2014/08/19 06:00 CRDT- 2014/04/25 06:00 PHST- 2014/04/25 06:00 [entrez] PHST- 2014/04/25 06:00 [pubmed] PHST- 2014/08/19 06:00 [medline] AID - ajpcell.00385.2013 [pii] AID - 10.1152/ajpcell.00385.2013 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2014 Jun 15;306(12):C1119-28. doi: 10.1152/ajpcell.00385.2013. Epub 2014 Apr 23.