Transforming growth factor-β1 regulates macrophage migration via RhoA
Abstract
Brief treatment with transforming growth factor (TGF)–β1 stimulated the migration of macrophages, whereas long-term exposure decreased their migration. Cell migration stimulated by TGF-β1 was markedly inhibited by 10 μg/mL Tat-C3 exoenzyme. TGF-β1 increased mRNA and protein levels of macrophage inflammatory protein (MIP)–1α in the initial period, and these effects also were inhibited by 10 μg/mL Tat-C3 and a dominant-negative (DN)–RhoA (N19RhoA). Cycloheximide, actinomycin D, and antibodies against MIP-1α and monocyte chemoattractant protein-1 (MCP-1) abolished the stimulation of cell migration by TGF-β1. These findings suggest that migration of these cells is regulated directly and indirectly via the expression of chemokines such as MIP-1α and MCP-1 mediated by RhoA in response to TGF-β1. TGF-β1 activated RhoA in the initial period, and thereafter inactivated them, suggesting that the inactivation of RhoA may be the cause of the reduced cell migration in response to TGF-β1 at later times. We therefore attempted to elucidate the molecular mechanism of the inactivation of RhoA by TGF-β1. First, TGF-β1 phosphorylated RhoA via protein kinase A, leading to inactivation of RhoA. Second, wild-type p190 Rho GTPase activating protein (p190RhoGAP) reduced and DN-p190RhoGAP reversed the reduction of cell migration induced by TGF-β, suggesting that it inactivated RhoA via p190 Rho GAP.
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High TGF-β1 expression inhibits migration of osteoclast precursors by suppressing RANKL expression and stimulating OPG production in osteoblasts.
“High TGF-β1 expression inhibits the migration of osteoclast precursors208 by suppressing RANKL expression and by stimulating OPG production in osteoblasts.209”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [208]
Cites
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534 · see citing works
Smad-dependent and Smad-independent pathways in TGF-β family signalling
Derynck, R., & Zhang, Y. E. (2003) · Nature · doi:10.1038/nature02006 · Cited by 5,370 · see citing works
Etienne‐Manneville, S., & Hall, A. (2002) · Nature · doi:10.1038/nature01148 · Cited by 4,796 · see citing works
Nobes, C. D., & Hall, A. (1995) · Cell · doi:10.1016/0092-8674(95)90370-4 · Cited by 4,414 · see citing works
Cellular and Molecular Immunology
Abbas, A. K., Lichtman, A. H., & Pillai, S. S. (1994) · Cited by 3,571 · see citing works
The two NF-κB activation pathways and their role in innate and adaptive immunity
Bonizzi, G., & Karin, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.03.008 · Cited by 2,535 · see citing works
TRANSFORMING GROWTH FACTOR-β REGULATION OF IMMUNE RESPONSES
Li, M. O., Wan, Y. Y., Sanjabi, S., Robertson, A.-K. L., & Flavell, R. A. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090737 · Cited by 2,199 · see citing works
REGULATION OF IMMUNE RESPONSES BY TGF-β
Letterio, J. J., & Roberts, A. B. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.137 · Cited by 1,894 · see citing works
Identification of Smad7, a TGFβ-inducible antagonist of TGF-β signalling
Nakao, A., Afrakhte, M., Morn, A., Nakayama, T., Christian, J. L., Heuchel, R. L., Itoh, S., Kawabata, M., Heldin, N., Heldin, C., et al. (1997) · Nature · doi:10.1038/39369 · Cited by 1,796 · see citing works
Actin-Based Cell Motility and Cell Locomotion
Mitchison, T. J., & Cramer, L. P. (1996) · Cell · doi:10.1016/s0092-8674(00)81281-7 · Cited by 1,538 · see citing works
Rho GTPases Control Polarity, Protrusion, and Adhesion during Cell Movement
Nobes, C. D., & Hall, A. K. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.144.6.1235 · Cited by 1,450 · see citing works
Kavsak, P., Rasmussen, R. K., Causing, C. G., Bonni, S., Zhu, H.-Q., Thomsen, G. H., & Wrana, J. (2000) · Molecules and Cells · doi:10.1016/s1097-2765(00)00134-9 · Cited by 1,449 · see citing works
Huynh, M.-L. N., Fadok, V., & Henson, P. (2002) · Journal of Clinical Investigation · doi:10.1172/jci11638 · Cited by 1,333 · see citing works
The Rho family GTPases RhoA, Racl , and CDC42Hsregulate transcriptional activation by SRF
Hill, C. S., Wynne, J., & Treisman, R. (1995) · Cell · doi:10.1016/s0092-8674(05)80020-0 · Cited by 1,269 · see citing works
Rho GTPases and cell migration
Ridley, A. J. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.15.2713 · Cited by 1,194 · see citing works
Bhowmick, N., Ghiassi, M., Bakin, A. V., Aakre, M., Lundquist, C., Engel, M., Arteaga, C., & Moses, H. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.1.27 · Cited by 1,087 · see citing works
Smad6 inhibits signalling by the TGF-β superfamily
Imamura, T., Takase, M., Nishihara, A., Oeda, E., Hanai, J., Kawabata, M., & Miyazono, K. (1997) · Nature · doi:10.1038/39355 · Cited by 1,023 · see citing works
Huynh, M.-L. N., Fadok, V. A., & Henson, P. M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0211638 · Cited by 957 · see citing works
Smad regulation in TGF-β signal transduction
Moustakas, A., Souchelnytskyi, S., & Heldin, C. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.24.4359 · Cited by 929 · see citing works
Ebisawa, T., Fukuchi, M., Murakami, G., Chiba, T., Tanaka, K., Imamura, T., & Miyazono, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100008200 · Cited by 845 · see citing works
ERK phosphorylation potentiates Elk‐1‐mediated ternary complex formation and transactivation.
Gille, H., Kortenjann, M., Thomae, O., Moomaw, C. R., Slaughter, C. A., Cobb, M. H., & Shaw, P. E. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07076.x · Cited by 665 · see citing works
Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins.Preprint
Perona, R., Montaner, S., Saniger, L., Sánchez‐Pérez, I., Bravo, R., & Lacal, J. C. (1997) · Genes & Development · doi:10.1101/gad.11.4.463 · Cited by 608 · see citing works
Lang, P., Gesbert, F., Delespine‐Carmagnat, M., Stancou, R., Pouchelet, M., & Bertoglio, J. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00383.x · Cited by 558 · see citing works
A Role for Cdc42 in Macrophage Chemotaxis
Allen, W. E., Zicha, D., Ridley, A. J., & Jones, G. E. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.5.1147 · Cited by 528 · see citing works
Edlund, S., Landström, M., Heldin, C., & Aspenström, P. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-08-0398 · Cited by 418 · see citing works
Transforming growth factor beta (TGF-?) in inflammation: A cause and a cure
Wahl, S. M. (1992) · Journal of Clinical Immunology · doi:10.1007/bf00918135 · Cited by 407 · see citing works
αvβ5 integrin recruits the CrkII–Dock180–Rac1 complex for phagocytosis of apoptotic cells
Albert, M. L., Kim, J.-I., & Birge, R. B. (2000) · Nature Cell Biology · doi:10.1038/35046549 · Cited by 377 · see citing works
Self-citationInduction of Inhibitory Smad6 and Smad7 mRNA by TGF-β Family Members
Afrakhte, M., Morén, A., Jossan, S., Itoh, S., Sampath, K. T., Westermark, B., Heldin, C., Heldin, N., & ten Dijke, P. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9170 · Cited by 353 · see citing works
Determination of GTP loading on Rho
Ren, X. D., & Schwartz, M. A. (2000) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(00)25448-7 · Cited by 342 · see citing works
Cox, E. A., Sastry, S. K., & Anna Huttenlocher, A. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.2.265 · Cited by 299 · see citing works
Montaner, S., Perona, R., Saniger, L., & Lacal, J. C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.12779 · Cited by 228 · see citing works
Brouns, M. R., Matheson, S. F., Hu, K., Delalle, I., Caviness, V. S., Silver, J., Bronson, R. T., & Settleman, J. E. (2000) · Development · doi:10.1242/dev.127.22.4891 · Cited by 225 · see citing works
Bidirectional regulation of macrophage function by TGF-β
Ashcroft, G. S. (1999) · Microbes and Infection · doi:10.1016/s1286-4579(99)00257-9 · Cited by 216 · see citing works
PKA inhibits RhoA activation: a protection mechanism against endothelial barrier dysfunction
Qiao, J., Huang, F., & Lum, H. (2003) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00429.2002 · Cited by 193 · see citing works
Forget, M.-A., Desrosiers, R. R., Gingras, D., & Béliveau, R. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3610243 · Cited by 176 · see citing works
Engulfment of Apoptotic Cells Is Negatively Regulated by Rho-mediated Signaling
Tosello‐Trampont, A., Nakada‐Tsukui, K., & Ravichandran, K. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306079200 · Cited by 153 · see citing works
Forget, M.-A., Desrosiers, R. R., Gingras, D. J., et al. (2002) · Biochemical Journal · doi:10.1042/bj3610243 · Cited by 140 · see citing works
Arsura, M., Panta, G. R., Bilyeu, J. D., Cavin, L. G., Sovak, M. A., Oliver, A. A., Factor, V. M., Heuchel, R. L., Mercurio, F., Thorgeirsson, S. S., et al. (2003) · Oncogene · doi:10.1038/sj.onc.1206132 · Cited by 139 · see citing works
Delgado, M., Jonakait, G. M., & Ganea, D. (2002) · Glia · doi:10.1002/glia.10098 · Cited by 131 · see citing works
Murthy, K. S., Zhou, H., Grider, J. R., et al. (2003) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00465.2002 · Cited by 129 · see citing works
Anchoring of both PKA and 14‐3‐3 inhibits the Rho‐GEF activity of the AKAP‐Lbc signaling complex
Diviani, D., Abuin, L., Cotecchia, S., & Pansier, L. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600287 · Cited by 125 · see citing works
A Transforming Growth Factor β-Induced Smad3/Smad4 Complex Directly Activates Protein Kinase A
Zhang, L., Duan, C. J., Binkley, C. E., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.5.2169-2180.2004 · Cited by 123 · see citing works
PKA phosphorylates the p75 receptor and regulates its localization to lipid rafts
Higuchi, H., Yamashita, T., Yoshikawa, H., & Tohyama, M. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg177 · Cited by 119 · see citing works
Shen, X., Li, J., Hu, P. P.-C., Waddell, D. S., Zhang, J., & Wang, X. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009534200 · Cited by 116 · see citing works
Maddala, R., Reddy, V. N., Epstein, D. L., & Rao, V. (2003) · PubMed · Cited by 107 · see citing works
Molecular Signaling Mechanisms of Cell Migration and Invasion
Stupack, D. G., Cho, S. Y., & Klemke, R. L. (2000) · Immunologic Research · doi:10.1385/ir:21:2-3:83 · Cited by 97 · see citing works
The Small GTP-Binding Protein Rho Potentiates AP-1 Transcription in T Cells
Chang, J., Pratt, J. C., Sawasdikosol, S., Kapeller, R., & Burakoff, S. J. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.9.4986 · Cited by 87 · see citing works
Molecular Regulation of Monocyte Chemoattractant Protein-1 Expression in Pancreatic β-Cells
Kutlu, B., Darville, M. I., Cardozo, A. K., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.2.348 · Cited by 87 · see citing works
Montaner, S., Perona, R., Saniger, L., & Lacal, J. C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.13.8506 · Cited by 83 · see citing works
Cheng, J., Encarnación, M. M. D., Warner, G. M., et al. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00153.2005 · Cited by 69 · see citing works
Fernández, N., Renedo, M., García‐Rodríguez, C., & Crespo, M. S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.6.3321 · Cited by 69 · see citing works
Imamichi, Y., Waidmann, O., Hein, R., Eleftheriou, P., Giehl, K., & Menke, A. (2005) · Biological Chemistry · doi:10.1515/bc.2005.028 · Cited by 59 · see citing works
Angiotensin II Participates in Hepatic Inflammation and Fibrosis through MCP-1 Expression
Kanno, K., Tazuma, S., Nishioka, T., Hyogo, H., & Chayama, K. (2005) · Digestive Diseases and Sciences · doi:10.1007/s10620-005-2669-7 · Cited by 46 · see citing works
Rho Is Involved in Superoxide Formation during Phagocytosis of Opsonized Zymosans
Kim, J.-S., Diebold, B. A., Kim, J., Kim, J., Lee, J., & Park, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308386200 · Cited by 39 · see citing works
Self-citationKim, J.-S., Kim, J. G., Jeon, C., Won, H.-Y., Moon, M., Seo, J.-Y., Kim, J., Kim, J., Lee, J.-Y., Choi, S.-Y., et al. (2005) · Experimental & Molecular Medicine · doi:10.1038/emm.2005.71 · Cited by 33 · see citing works
Self-citationPark, J., Kim, J.-S., Jung, K., et al. (2003) · Molecules and Cells · doi:10.1016/s1016-8478(23)13791-5 · Cited by 30 · see citing works
Self-citationMériane, M., Charrasse, S., Comunale, F., et al. (2002) · Biology of the Cell · doi:10.1016/s0248-4900(02)00023-0 · Cited by 28 · see citing works
Pozo, D., Guerrero, J. M., & Calvo, J. R. (2002) · Cytokine · doi:10.1006/cyto.2002.1024 · Cited by 22 · see citing works
Cheng, L. M., Yan, Y., & Wang, Q. R. (2003) · Cell Biology International · doi:10.1016/s1065-6995(03)00144-6 · Cited by 6 · see citing works
Settleman, J. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00103-6 · Cited by 4 · see citing works
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Xu, X., Zheng, L., Yuan, Q., Zhen, G., Crane, J. L., Zhou, X., & Cao, X. (2018) · Bone Research · doi:10.1038/s41413-017-0005-4 · Cited by 414 · see citing works
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- Authors
- Kim, J.-S., Kim, J.-G., Moon, M.-Y., Jeon, C.-Y., Won, H.-Y., Kim, H.-J., Jeon, Y.-J., Seo, J.-Y., Kim, J.-I., Kim, J., Lee, J.-Y., Kim, P.-H., & Park, J.-B.
- Affiliations
- Hallym University (KR)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-09-15
- Volume
- 108
- Issue
- 6
- Pages
- 1821-1829
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2093833484
- Cited by
- 134
- References
- 60
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 13 · 2022: 11 · 2021: 5 · 2020: 8 · 2019: 12 · 2018: 9 · 2017: 9 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 8 · 2012: 5
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- University of Ulsan
- Hallym University
- University of California, San Francisco
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- TGF-β1, macrophage migration, RhoA, chemokines, MIP-1α, MCP-1, protein kinase A, chemotaxis
- MeSH terms
- Animals, Base Sequence, Carrier Proteins, Cell Line, Cell Movement, Chemotaxis, DNA-Binding Proteins, Humans, Macrophage Activation, Macrophages, Models, Biological, Repressor Proteins, RNA, Messenger, Gene Expression, Transforming Growth Factor beta, Cyclic AMP-Dependent Protein Kinases, HL-60 Cells, Macrophage Inflammatory Proteins, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, rho GTP-Binding Proteins, rhoA GTP-Binding Protein, Mice, Transforming Growth Factor beta1, Chemokine CCL3, Chemokine CCL4
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