Transcription factor EGR-1 transactivates the MMP1 gene promoter in response to TNFα in HaCaT keratinocytes
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNFα is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNFα-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP1) sites. Assessments of the 5’-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNFα. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNFα-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNFα-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNFα-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression.
Abstract
Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNFα is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNFα-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP1) sites. Assessments of the 5’-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNFα. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNFα-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNFα-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNFα-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression.
참고문헌 (27)
- Loffek S, "Series"matrix metalloproteinases in lung health and disease" : Biological role of matrix metalloproteinases : a critical balance", Eur Respir J, 38, pp.191~208 (2011)
- Panwar P, "Aging-associated modifications of collagen affect its degradation by matrix metalloproteinases", Matrix Biol, 65, pp.30~44 (2018)
- Fanjul-Fernandez M, "Matrix metalloproteinases : evolution, gene regulation and functional analysis in mouse models", Biochim Biophys Acta, 1803, pp.3~19 (2010)
- Page-McCaw A, "Matrix metalloproteinases and the regulation of tissue remodelling", Nat Rev Mol Cell Biol, 8, pp.221~233 (2007)
- Ala-aho R, "Collagenases in cancer", Biochimie, 87, pp.273~286 (2005)
- Bashir MM, "TNF-alpha production in the skin", Arch Dermatol Res, 301, pp.87~91 (2009)
- Gashler A, "Early growth response protein 1(Egr-1) : prototype of a zinc-finger family of transcription factors", Prog Nucleic Acid Res Mol Biol, 50, pp.191~224 (1995)
- Shin SY, "Transcriptional regulation of the growth-regulated oncogene alpha gene by early growth response protein-1 in response to tumor necrosis factor alpha stimulation", Biochim Biophys Acta, 1829, pp.1066~1074 (2013)
- Grimbacher B, "TNF-alpha induces the transcription factor Egr-1, proinflammatory cytokines and cell proliferation in human skin fibroblasts and synovial lining cells", Rheumatol Int, 17, pp.185~192 (1998)
- Okada M, "Extinguishing Egr-1-dependent inflammatory and thrombotic cascades after lung transplantation", FASEB J, 15, pp.2757~2759 (2001)
- Ji B, "Pancreatic gene expression during the initiation of acute pancreatitis : identification of EGR-1 as a key regulator", Physiol Genomics, 14, pp.59~72 (2003)
- Ko SW, "Selective contribution of Egr1(zif", 268)to persistent inflammatory pain, 2005, pp.6, 12~20
- Cho SJ, "Role of early growth response-1(Egr-1)in interleukin-13-induced inflammation and remodeling", J Biol Chem, 281, pp.8161~8168 (2006)
- Son SW, "Regulatory mechanism of TNFalpha autoregulation in HaCaT cells : the role of the transcription factor EGR-1", Biochem Biophys Res Commun, 374, pp.777~782 (2008)
- Jeong SH, "Egr-1 is a key regulator of IL-17A-induced psoriasin upregulation in psoriasis", Exp Dermatol, 23, pp.890~895 (2014)
- Ryu WI, "IL-33 induces Egr-1-dependent TSLP expression via the MAPK pathways in human keratinocytes", Exp Dermatol, 24, pp.857~863 (2015)
- Shin SY, "Transcription factor Egr-1 is essential for maximal matrix metalloproteinase-9 transcription by tumor necrosis factor alpha", Mol Cancer Res, 8, pp.507~519 (2010)
- Kim J, "Leptin is a direct transcriptional target of EGR1 in human breast cancer cells", Mol Biol Rep, 46, pp.317~324 (2019)
- Sun Y, "Basic calcium phosphate crystals induce matrix metalloproteinase-1 through the Ras", mitogen-activated protein kinase, AP-1, pp.metalloproteinase 1 pathway. Involvement of transcription factor binding sites AP-1 and PEA-3, J Biol Chem[DOI]
- Westermarck J, "Differential regulation of interstitial collagenase(MMP-1)gene expression by ETS transcription factors", Oncogene, 14, pp.2651~2660 (1997)
- Nakashima A, "Interactions between Egr1 and AP1 factors in regulation of tyrosine hydroxylase transcription", Brain Res Mol Brain Res, 112, pp.61~69 (2003)
- Utreras E, "Tumor necrosis factor-alpha regulates cyclin-dependent kinase 5activity during pain signaling through transcriptional activation of p35", J Biol Chem, 284, pp.2275~2284 (2009)
- Mishra JP, "Differential involvement of calmodulin-dependent protein kinase II-activated AP-1 and c-Jun N-terminal kinaseactivated EGR-1 signaling pathways in tumor necrosis factor-alpha and lipopolysaccharide-induced CD44 expression in human monocytic cells", J Biol Chem, 280, pp.26825~26837 (2005)
- Son SW, "Regulatory mechanism of TNFalpha autoregulation in HaCaT cells : the role of the transcription factor EGR-1", Biochem Biophys Res Commun, 374, pp.777~782 (2008)
- Segawa R, "EGFR transactivation is involved in TNF-alpha-induced expression of thymic stromal lymphopoietin in human keratinocyte cell line", J Dermatol Sci, 89, pp.290~298 (2018)
- Kim SH, "Egr1 regulates lithium-induced transcription of the Period 2(PER2)gene", Biochim Biophys Acta, 1832, pp.1969~1979 (2013)
- 민동영, "Leptin stimulates IGF-1 transcription by activating AP-1 in human breast cancer cells", BMB Reports, 52(6), pp.385~390 (2019), 생화학분자생물학회[DOI]