Fli1 and Tissue Fibrosis in Various Diseases
Abstract
1. Introduction
2. Diseases Associated with Fli1 Deficiency
2.1. Fli1 in Systemic Sclerosis
2.2. Fli1 in Uremic Cardiomyopathy
2.3. Fli1 in Preeclampsia
2.4. Fli1 as a Common Causative Factor of Hypertension
Expression | Effect | Experimental System | References | |
---|---|---|---|---|
Fli1 repressors | ||||
TGF-β | ↑ | Activation of TGF-β receptors | Human dermal fibroblasts; rat diabetes model; rat hypertension model | [25,29,32,38,39,79,80,81] |
c-Abl | ↑ | PKC-δ phosphorylation | Human normal and SSc dermal fibroblasts | [40,41,47,51] |
PKC-δ | ↑ | Fli1 phosphorylation | Human normal and SSc dermal fibroblasts; FLI1-transfected HEK293T cells; FLI1 silencing in human UA | [37,39,42,47,77] |
Endothelin-1 | ↑ | Fli1 activation | Human normal and SSc dermal fibroblasts; BLM-treated mice | [42] |
PCAF | ↑ | Fli1 acetylation | Human dermal fibroblasts; FLI1-transfected HEK293T cells | [38] |
CXCL4 | ↑ | Vasculopathy | HUVECs | [51] |
MBG | ↑ | PKC-δ activation; Fli1 suppression | Wild-type and FLI1-knockdown mice; rat CKD model; rat cardiac fibroblasts; human cardiac fibroblasts; human renal fibroblasts; FLI1-transfected renal fibroblasts; rat diabetes model; rat hypertension model; rat PE model | [16,66,67,68,73,74,75,76,77,79,80,81] |
Fli1-deficiency targets | ||||
COL1 | ↑ | Collagen synthesis | FLI1-transfected human dermal fibroblasts; human normal and SSc dermal fibroblasts; murine Fli11−/−, Fli1+/− and Fli1+/+ fibroblasts; wild-type and FLI1-knockdown mice; rat CKD model; rat cardiac fibroblasts; human cardiac fibroblasts; human renal fibroblasts; FLI1-transfected renal fibroblasts; rat diabetes model; rat hypertension model; rat PE model; human PE UA; FLI1 silencing in human UA; human MBG-treated UA | [8,16,25,29,32,38,66,67,68,73,74,75,76,77,79,80,81] |
CTGF(CCN2) | ↑ | COL1A1 and COL1A2 upregulation; MMP-1 downregulation | FLI1-transfected human dermal fibroblasts; human SSc fibroblasts | [32,33] |
MMP-1 | ↓ | Increased production of EMC components | FLI1-transfected human dermal fibroblasts; human SSc fibroblasts | [32,33] |
Fibronectin | ↑ | Fibrosis | Human CD14+ monocytes and CD14+ macrophages | [23] |
Chemerin | ↑ | Impaired angiogenesis | Human SSc dermal vessels and HDMECs; murine Fli1+/− dermal blood vessels; | [35] |
S100A12 | ↑ | Skin sclerosis | Human SSc skin; | [36] |
RALDH1 | ↓ | Fibrosis | Human dermal dendritic cells; BLM-treated Fli1+/− mice | [30] |
Cathepsin B | ↑ ↓ | Vasculopathy Increased production of EMC components | FLI1 silencing in HDMECs; Fli1+/− mice; human dcSSc dermal fibroblasts, early dcSSc dermal fibroblasts | [43] |
Cathepsin L | ↑ ↓ | Vasculopathy Increased production of EMC components | FLI1 silencing in HDMECs; human SS dermal vessels and skin; FLI1-knockout mice; skin of BLM-treated mice | [45] |
Cathepsin V | ↓ | Increased production of EMC components | FLI1 silencing in HDMECs; human dcSSc dermal fibroblasts, microvascular ECs, dcSSc and lcSSc skin keratinocytes | [44] |
PGRN | ↑ | Inflammation; skin sclerosis; fibrosis | Human SSc dermal fibroblasts; Fli-1+/− mice; BLM-treated mice; human LSc skin lesions | [46,47] |
TNF-α | ↑ | Inflammation; fibrosis | Human LSc skin lesions; | [47] |
CXCL5 | ↓ | Vasculopathy | Human dcSSc dermal blood vessels; FLI1 silencing in HDMECs; dermal vessels of Fli1 knockout mice | [48] |
CXCL6 | ↑ | Tissues fibrosis; vasculopathy | Human SSc dermal fibroblasts; FLI1 silencing in HDMECs | [49] |
CCL20 | ↑ | Fibrosis | Human early dcSSc | [52] |
CCL6 | ↑ | Vasculopathy | Human SSc dermal vessels; FLI1 silencing in HDMECs | [52] |
EPCR | ↓ | Impaired vascular homeostasis | Human SSc dermal vessels; Fli1+/− mice; FLI1 silencing in HDMECs | [53] |
VE-cadherin | ↓ | Impaired vascular homeostasis | MDMECs of Fli1 CKO mice; MDMECs of Fli1+/− mice; FLI1 silencing in HDMECs | [34] |
PECAM-1 | ↓ | Impaired vascular homeostasis | MDMECs of Fli1 CKO mice; MDMECs of Fli1+/− mice; FLI1 silencing in HDMECs | [34] |
MMP-9 | ↓ | Impaired vascular homeostasis | MDMECs of Fli1 CKO mice; MDMECs of Fli1+/− mice; FLI1 silencing in HDMECs | [34] |
PDGF-B | ↓ | Impaired vascular homeostasis | MDMECs of Fli1 CKO mice; MDMECs of Fli1+/− mice; FLI1 silencing in HDMECs | [34] |
S1P1 | ↓ | Impaired vascular homeostasis | MDMECs of Fli1 CKO mice; MDMECs of Fli1+/− mice; FLI1 silencing in HDMECs | [34] |
Adipsin | ↑ | Vascular hypertension | Human SSc dermal vessels; FLI1 silencing in HDMECs | [54] |
Genetic and epigenetic factors | ||||
(GA)n alleles | ↑ | Increased susceptibility to SSc | Human SSc peripheral blood | [56] |
Acetylation of histones H3 and H4 in the FLI1 gene promoter | ↓ | FLI1 suppression; increased collagen synthesis | Human skin, normal and dcSSc fibroblasts | [57] |
HDAC-1 and 6 | ↑ | FLI1 suppression | Human skin, normal and dcSSc fibroblasts | [57] |
MBD-1 and 2, MeCP2 | ↑ | DNA methylation | Human skin, normal and dcSSc fibroblasts | [57] |
Methylation of CpG islands in the FLI1 promoter | ↑ | FLI1 suppression; increased Collagen synthesis | Human skin, normal and dcSSc fibroblasts | [57] |
DNMT1 | ↑ | FLI1 suppression | Human skin, normal and dcSSc fibroblasts | [33,57] |
COL23A1, COL4A2 methylation | ↓ | Increased collagen synthesis | Human dcSSc and lcSSc dermal fibroblasts | [58] |
ITGA9 methylation | ↓ | TGF-β upregulation | Human dcSSc and lcSSc dermal fibroblasts | [58] |
ADAM12 methylation | ↓ | TGF-β upregulation | Human dcSSc and lcSSc dermal fibroblasts | [58] |
miRNA-26a | ↑ | FLI1 suppression | Primary SSc skin fibroblasts | [31] |
miRNA-21 | ↑ | TGF-β upregulation; collagen synthesis | Human dcSSc and TGF-β treated normal fibroblasts | [59] |
miRNA-29a | ↓ | TGF-β upregulation; collagen synthesis | Human dcSSc and TGF-β treated normal fibroblasts | [59] |
3. Fli1 Overexpression as a Cause of Ewing’s Sarcoma
4. Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Expression | Effect | Experimental System | References | |
---|---|---|---|---|
Tenascin-C (TNC) | ↑ | ECM growth | FLI1 transfection of human fibrosarcoma HT-1080 cells; human primary ES tumors; TNC-knockout cell lines; murine xenografts | [86,87,94] |
ERK1/2 protein kinases | ↑ | Tumor growth; metastases; dysregulation of EMC metabolism | NIH-3T3 cells; human ES cell lines | [87,95] |
Caveolin-1 (CAV1) | ↑ | Tumor growth; metastases; | Human ES cell lines; CAV1 silencing; murine xenografts | [96] |
MMP-9 | ↑ | Tumor growth; metastases; dysregulation of EMC metabolism | Human ES cell lines; CAV1 silencing; murine xenografts | [96] |
LOX | ↓ | Tumorigenesis | Human ES cell lines; murine xenografts | [97] |
Wnt/β-catenin/TGF-β/SMAD | ↑ | Altered synthesis of ECM proteins; promotion of angiogenesis in local TME | Human ES cells; HUVECs; FLI1 knockdown | [98] |
DNA methylation | ↓ | Tumorigenesis | Human ES cell lines; primary pediatric MSC; FLI1 knockdown; in vivo tumorigenesis | [99] |
Histone acetylation, H3K4Me3, H3K9ac, H3K27ac markers at the FLI1 promoter | ↑ | FLI1 transcriptional activation; tumorigenesis | Human ES cell lines; primary pediatric MSC; primary tumor cells; FLI1 knockdown; in vivo tumorigenesis | [99,100] |
Acetyltransferase p300 | ↑ | Tumorigenesis | Human ES cell lines; primary pediatric MSC; FLI1 knockdown; in vivo tumorigenesis | [99] |
Cyclin G1, Cyclin D1 | ↑ | Tumorigenesis | Human SK-N-MC and PNKT-1 cell lines; murine xenografts; FLI1 transfected NIH3T3 cell | [101] |
NR0B1 | ↑ | Increased ES susceptibility | ES A673 and HEK 293EBNA cell lines; FLI1 knockdown | [92] |
Histone methyltransferase EZH2 | ↑ | Tumor development; metastases growth | ES and neuroblastoma cell lines; murine xenografts; RNA interference; FLI1 transfection | [102] |
HOX genes | ↑ | Aberrant differentiation; tumorigenesis | ES cell lines; HeLa, neuroblastoma, HEK293FT, NCSC, BM-MSCs; FLI1 transduction of NCSC | [103] |
miRNA-145 | ↓ | Tumorigenesis | hpMSCs; MSC; ES cell lines; mouse xenografts | [104] |
miRNA-22 | ↓ | Tumor growth | ES A673 cells; miRNA-22 overexpression; murine xenografts | [105] |
miRNA-214-3p | ↓ | Tumor growth | ES cell lines; human BM-MSCs; human ES primary tumors and metastases; FLI1 silencing | [106] |
miRNA-let-7g | ↓ | Tumorigenesis | MSCs; ES cell lines; murine xenografts; FLI1 knockdown | [107] |
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Mikhailova, E.V.; Romanova, I.V.; Bagrov, A.Y.; Agalakova, N.I. Fli1 and Tissue Fibrosis in Various Diseases. Int. J. Mol. Sci. 2023, 24, 1881. https://doi.org/10.3390/ijms24031881
Mikhailova EV, Romanova IV, Bagrov AY, Agalakova NI. Fli1 and Tissue Fibrosis in Various Diseases. International Journal of Molecular Sciences. 2023; 24(3):1881. https://doi.org/10.3390/ijms24031881
Chicago/Turabian StyleMikhailova, Elena V., Irina V. Romanova, Alexei Y. Bagrov, and Natalia I. Agalakova. 2023. "Fli1 and Tissue Fibrosis in Various Diseases" International Journal of Molecular Sciences 24, no. 3: 1881. https://doi.org/10.3390/ijms24031881
APA StyleMikhailova, E. V., Romanova, I. V., Bagrov, A. Y., & Agalakova, N. I. (2023). Fli1 and Tissue Fibrosis in Various Diseases. International Journal of Molecular Sciences, 24(3), 1881. https://doi.org/10.3390/ijms24031881