The PTEN/PI3K/Akt signaling pathway mediates HMGB1-induced cell proliferation by regulating the NF-κB/cyclin D1 pathway in mouse mesangial cells.
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-κB (NF-κB) pathway using pyrrolidine dithiocarbamate (PDTC) and SN50, inhibitors of NF-κB, 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-κB signaling pathway.
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and.
Xiao-Juan
XJ
Feng
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and.
Shu-Xia
SX
Liu
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and.
Chao
C
Wu
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and.
Peng-Peng
PP
Kang
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and.
Qing-Juan
QJ
Liu
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and.
Jun
J
Hao
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and.
Hong-Bo
HB
Li
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and.
Fan
F
Li
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and.
Yu-Jun
YJ
Zhang
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and.
Xiao-Hui
XH
Fu
Department of Hand and Foot Surgery, Third Hospital of Shijiazhuang City, Shijiazhuang, China.
San-Bing
SB
Zhang
Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; and zlf9205@126.com.
Lian-Fu
LF
Zuo
D000818:Animals; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D008181:Lupus Nephritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050527:Mesangial Cells / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics
D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D016328:NF-kappa B; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
Akt; HMGB1; NF-κB; PTEN; cell proliferation; mouse mesangial cell