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Mol. Cells 2011; 31(3): 225-230

Published online January 6, 2011

https://doi.org/10.1007/s10059-011-0023-9

© The Korean Society for Molecular and Cellular Biology

Tissue Inhibitor of Metalloproteinase-1 Pro-motes NIH3T3 Fibroblast Proliferation by Activating p-Akt and Cell Cycle Progression

Yang Lu1,5, Shuxin Liu 2,5, Shujia Zhang1,3, Guangyan Cai1, Hongwei Jiang4, Huabin Su1, Xiaofan Li1, Quan Hong1, Xueguang Zhang1, and Xiangmei Chen1,*

1Department of Nephrology, Kidney Center and Key Lab of the People’s Liberation Army (PLA), General Hospital of PLA, Beijing, China, 2Dalian Municipal Central Hospital, Dalian, China, 3Department of Nephrology, 1st Hospital of Haerbin, China, 4Department of Endocrinology and Metabolism, 1st Affiliated Hospital, Henan University of Science and Technology, Luoyang, China, 5These authors contributed equally to this work.

Correspondence to : *Correspondence: xmchen301@126.com

Received: July 28, 2010; Revised: November 9, 2010; Accepted: November 24, 2010

Abstract

Tissue inhibitor of metalloproteinase-1 (TIMP-1) plays various roles in cell growth in different cell types. However, few studies have focused on TIMP-1’s effect on fibroblast cells. In this study, we investigated the effects of TIMP-1 overexpression on NIH3T3 fibroblast proliferation and potential transduction signaling pathways involved. Overexpression of TIMP-1, by transfection of the pLenti6/ V5-DEST-TIMP-1 plasmid, significantly promoted NIH3T3 proliferation as determined by the BrdU array. Neither 5 nor 15 nM GM6001 (matrix metalloproteinase system inhibitor) af-fected NIH3T3 proliferation, but 45 nM GM6001 inhibited proliferation. TIMP-1 overexpression activated the p-Akt pathway, but not the p-ERK or p-p38 pathway. In TIMP-1-transfected cells, cyclinD1 was upregulated and p21CIP1 and p27KIP1 were downregulated, which promoted cell entry into the S and G2/M phases. The PI3-K inhibitor LY294002 abolished the TIMP-1-induced effects. Overex-pression of intracellular TIMP-1 stimulated NIH3T3 fibroblast proliferation in a matrix metalloproteinase (MMP)-indepen-dent manner by activating the p-Akt pathway and related cell cycle progression.

Keywords Akt, cell cycle, NIH3T3 cells, proliferation, tissue inhibitor of metalloproteinase-1 (TIMP-1)

Article

Research Article

Mol. Cells 2011; 31(3): 225-230

Published online March 31, 2011 https://doi.org/10.1007/s10059-011-0023-9

Copyright © The Korean Society for Molecular and Cellular Biology.

Tissue Inhibitor of Metalloproteinase-1 Pro-motes NIH3T3 Fibroblast Proliferation by Activating p-Akt and Cell Cycle Progression

Yang Lu1,5, Shuxin Liu 2,5, Shujia Zhang1,3, Guangyan Cai1, Hongwei Jiang4, Huabin Su1, Xiaofan Li1, Quan Hong1, Xueguang Zhang1, and Xiangmei Chen1,*

1Department of Nephrology, Kidney Center and Key Lab of the People’s Liberation Army (PLA), General Hospital of PLA, Beijing, China, 2Dalian Municipal Central Hospital, Dalian, China, 3Department of Nephrology, 1st Hospital of Haerbin, China, 4Department of Endocrinology and Metabolism, 1st Affiliated Hospital, Henan University of Science and Technology, Luoyang, China, 5These authors contributed equally to this work.

Correspondence to:*Correspondence: xmchen301@126.com

Received: July 28, 2010; Revised: November 9, 2010; Accepted: November 24, 2010

Abstract

Tissue inhibitor of metalloproteinase-1 (TIMP-1) plays various roles in cell growth in different cell types. However, few studies have focused on TIMP-1’s effect on fibroblast cells. In this study, we investigated the effects of TIMP-1 overexpression on NIH3T3 fibroblast proliferation and potential transduction signaling pathways involved. Overexpression of TIMP-1, by transfection of the pLenti6/ V5-DEST-TIMP-1 plasmid, significantly promoted NIH3T3 proliferation as determined by the BrdU array. Neither 5 nor 15 nM GM6001 (matrix metalloproteinase system inhibitor) af-fected NIH3T3 proliferation, but 45 nM GM6001 inhibited proliferation. TIMP-1 overexpression activated the p-Akt pathway, but not the p-ERK or p-p38 pathway. In TIMP-1-transfected cells, cyclinD1 was upregulated and p21CIP1 and p27KIP1 were downregulated, which promoted cell entry into the S and G2/M phases. The PI3-K inhibitor LY294002 abolished the TIMP-1-induced effects. Overex-pression of intracellular TIMP-1 stimulated NIH3T3 fibroblast proliferation in a matrix metalloproteinase (MMP)-indepen-dent manner by activating the p-Akt pathway and related cell cycle progression.

Keywords: Akt, cell cycle, NIH3T3 cells, proliferation, tissue inhibitor of metalloproteinase-1 (TIMP-1)

Mol. Cells
May 31, 2023 Vol.46 No.5, pp. 259~328
COVER PICTURE
The alpha-helices in the lamin filaments are depicted as coils, with different subdomains distinguished by various colors. Coil 1a is represented by magenta, coil 1b by yellow, L2 by green, coil 2a by white, coil 2b by brown, stutter by cyan, coil 2c by dark blue, and the lamin Ig-like domain by grey. In the background, cells are displayed, with the cytosol depicted in green and the nucleus in blue (Ahn et al., pp. 309-318).

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