Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review
Abstract
:1. Introduction
2. Methods—Literature Search Strategy
3. (Phyto)Estrogen Signaling in Wound Healing and Skin Aging
4. Inflammatory Phase and Oxidative Stress
5. Proliferation Phase
5.1. Fibroblasts
5.2. Angiogeneis
5.3. Epidermis Regeneration
6. Maturation and Remodeling Phase
7. Discussion and Conclusions
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AMPK | Adenosine monophosphate-activated protein kinase |
AP-1 | Activator protein 1 |
BCRP | Breast cancer resistance protein |
bFGF | Basic fibroblast growth factor |
Bcl-2 | B-cell lymphoma 2 |
BMECs | Brain microvascular endothelial cells |
CCL | C-C motif chemokine |
CD | Cluster of differentiation |
COL18A1 | Collagen Type XVIII Alpha 1 Chain |
CTGF | Connective tissue growth factor |
CXCL | C-X-C motif chemokine ligand |
ECM | Extracellular matrix |
EGF | Epidermal growth factor |
eNOS | Endothelial nitric oxide synthase |
ER | Estrogen receptor |
ERK | Signal-regulated kinase |
ERT | Estrogen replacement therapy |
FoxO1 | Orkhead box O transcription factor 1 |
GPR30 | G protein-coupled receptor 30 |
GSH | Glutathione |
GT | Granulation tissue |
HaCaT | Human keratinocyte cell line |
HMVEC-d | Human dermal microvascular vein endothelial cells |
HUVEC | Human umbilical vein endothelial cell |
ICAM-1 | Intercellular adhesion molecule 1 |
IGF | Insulin growth factor |
IL | Interleukin |
iNOS | Inducible nitric oxide synthase |
ITGB3 | Integrin β3 |
JAK | Januse kinase |
LPC | Lysophosphatidylcholine |
LPS | Lipopolysaccharide |
MAPK | Mitogen-activated protein kinase |
MCF-7 | Michigan Cancer Foundation-7 |
MCP-1 | Monocyte chemoattractant protein-1 |
MMP | Matrix metalloproteinase |
MyD88 | Myeloid differentiation factor 88 |
NF-κB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
NLRP3 | NOD-like receptor protein-3 |
OVX | Ovariectomized |
ox-LDL | Oxidized low density lipoprotein |
PDGF | Platelet-derived growth factor |
PTK | Protein tyrosine kinase |
ROS | Reactive oxygen species |
SMA | Smooth muscle actin |
SMAD | Sma and MAD-related protein 3 |
SERM | Selective estrogen receptor modulator |
STAT-1 | Signal transducer and activator of transcription 1 |
TIMP | Tissue inhibitor of matrix metalloproteinase |
TG2 | Transglutaminase 2 |
TGF | Transforming growth factor |
TNF | Tumor necrosis factor |
t-BHP | t-Butylhydroperoxide |
uPA | Urokinase-type plasminogen activator |
VEGF | Vascular endothelial growth factor |
VEGFR | Vascular endothelial growth factor receptor |
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Phase of Wound Healing | Target Cell | Effect | Reference |
---|---|---|---|
Inflammation | Macrophage | ↓ activation of NF-κB, STAT-1, iNOS, AMPK | [43,48,49] |
↑ expression of NLRP3 | [45,46] | ||
↓ expression of TNF-α, NF-κB, Il6, IL-1β | [46,47,48] | ||
M1 → M2 shift promotion | [48] | ||
T cell, | ↓ infiltration | [53] | |
Granulocyte | ↓ infiltration | [54] | |
HUVEC | ↓ expression of NF-κB, TNF-α, E-selectin, P-selectin, MCP-1, IL-1β, IL-8, VCAM-1, ICAM-1 | [55,56] | |
HDMEC | ↑ activity of SOD | [59,60] | |
↑ expression of Bcl-2 | [59,60] | ||
Fibroblast | ↑ levels of GSH | [58] | |
↓ expression of MMP-1, MMP-9 | [58] | ||
↓ release of NO, ROS | [58] | ||
Keratinocyte | ↓ expression of TNF-α, IL-6, IL-23, MMP-1, MMP-9 | [57,58] | |
↑ levels of GSH | [58] | ||
↓ release of NO, ROS | [58] | ||
Proliferation | Fibroblast | ↑/↓ (low/high c) production of collagen | [74] |
↓ activity and production of uPA | [76] | ||
↓ activation of JNK, ERK1/2 | [76] | ||
HUVEC | ↓ proliferation | [83] | |
↓ expression of VEGF, VEGFR | [83,84] | ||
↑ signaling of MAPK | [33] | ||
↓ signaling of PTK | [33] | ||
↓ activation of c-Jun, JNK, p38 | [33,103] | ||
↓ production/activation of MMP-2, MMP-9 | [33,84] | ||
↓ VEFG/bFGF-induced expression of MMP-1, uPA and activation of MMP-2 | [85,86] | ||
↑/↓ (low/high dose) stimulation of sprouting | [62] | ||
↑ (low dose) secretion of bFGF, EGF, angiogenin, angiopoietin-2, MMP-9 and uPA receptor | [88] | ||
↓ cell-cell adhesion, migration | [91,94] | ||
↓ expression of VE-cadherin, connexin 43, integrin αV, multimerin | [91] | ||
↓ TNF-α induced expression of MCP-1, IL-8, sICAM-1, sVCAM-1, E-selectin | [93] | ||
↓ signaling of FAK/paxillin | [94] | ||
↑ restores expression of VEGF, TGF-β1, TG2 in estrogen deficiency | [90] | ||
BMEC | ↓ expression of MCP-1, ICAM-1 | [92] | |
Keratinocyte | ↑ proliferation | [99] | |
↑ signaling of ERk/Akt | [99] | ||
↑ production of hyaluronic acid | [100] | ||
↓ expression of FOS-B | [103] | ||
↑ expression of Bcl-2 | [60,104] | ||
Maturation | Fibroblast | ↓ proliferation/collagen production in hypertrophic scars | [28] |
↓ signaling of MAPK/ERK in hypertrophic scars | [28] | ||
↑ expression of C-JUN, C-FOS in keloid fibroblasts | [103] | ||
↓ expression of CTGF, TGF-β(1, 2, 3) in keloid fibroblasts | [104] |
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Čoma, M.; Lachová, V.; Mitrengová, P.; Gál, P. Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review. Curr. Issues Mol. Biol. 2021, 43, 127-141. https://doi.org/10.3390/cimb43010011
Čoma M, Lachová V, Mitrengová P, Gál P. Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review. Current Issues in Molecular Biology. 2021; 43(1):127-141. https://doi.org/10.3390/cimb43010011
Chicago/Turabian StyleČoma, Matúš, Veronika Lachová, Petra Mitrengová, and Peter Gál. 2021. "Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review" Current Issues in Molecular Biology 43, no. 1: 127-141. https://doi.org/10.3390/cimb43010011