Table 1.
Tumor-associated protein biomolecules differentially expressed in keloids
| Biomolecules | Abbreviation | Involved physiological function | Expression in keloids | Associated biological processes in keloids | Reference |
|---|---|---|---|---|---|
| Proliferation and apoptosis | |||||
| Catenin (Cadherin-associated protein), beta 1 | β-Catenin | Cell growth Cell adhesion |
Up-regulated | Maintenance of skin fibrosis | [51, 52, 54] |
| B-Cell lymphoma-2 | BCL2 | Programmed cell death | Positive in keratinocytes and fibroblasts | Blocked fibroblast apoptosis | [48] |
| Proto-oncogene C-Fos | C-FOS | Transactivating factor | Positive in dermal fibroblasts | Regulation of fibroblast proliferation | [48] |
| Calcitonin gene-related peptide | CGRP | Vasodilation | Up-regulated | Gene expression of growth factors in fibroblasts | [46] |
| c-Myc transcription factor | cMYC | Cell cycle progression Cellular transformation Apoptosis |
Down-regulated | Apoptosis | [47] |
| Proto-oncogene C-Jun | C-JUN | Transactivating factor | Positive in dermal fibroblasts | Regulation of fibroblast proliferation | [48] |
| Defender against cell death 1 | DAD-1 | Programmed cell death | Down-regulated | Apoptosis | [47] |
| Nineteen Kd interacting protein-3 | NIP3 | Pro-apoptotic factor | Down-regulated | Apoptosis | [47] |
| Tumor protein P53 | TP53 | Cell cycle arrest DNA repair Senescence |
Down-regulated | Decreased fibroblast proliferation | [48, 50] |
| Tumor protein P63 | TP63 | Maintenance of epithelial self-renewal | Up-regulated | Blockade of TP53 activity | [50] |
| Tumor necrosis factor receptor type 1-associated death domain protein | TRADD | Programmed cell death | Down-regulated | Apoptosis | [47] |
| Wingless-type MMTV integration site family, member 5A | Wnt5A | Proliferation Apoptosis Differentiation |
Up-regulated | Proliferation of fibroblasts | [52] |
| Wingless-type MMTV integration site family, member 10A | Wnt10A | Proliferation Apoptosis Differentiation |
Up-regulated | Proliferation of keloid progenitor cells | [53] |
| Collagen deposition and extracellular matrix formation | |||||
| Collagen type I alpha 1 chain | COLIα1 | Type I collagen synthesis | Up-regulated | Collagen synthesis | [71] |
| Heat shock protein 27 | HSP27 | Correct folding of proteins | Up-regulated | Matrix synthesis | [76] |
| Heat shock protein 47 | HSP47 | Collagen biosynthesis | Up-regulated | Synthesis and secretion of collagen | [76] |
| Interleukin 6 | IL-6 | Inflammation Maturation of B cells |
Up-regulated | Increased accumulation of ECM Regulation of fibroblast migration Regulation of matrix metalloproteinase function |
[60, 65] |
| Integrin subunit alpha 2 | ITGα2 | Modulation of collagenase gene expression Organization of newly synthesized ECM |
Up-regulated | Matrix synthesis | [46] |
| Matrix metalloproteinase 2 | MMP-2 | Cleaving components of the ECM Cleaving molecules involved in signal transduction |
Up-regulated | Remodeling of collagen bundle regions Degradation of ECM |
[67, 68] |
| Matrix metalloproteinase 13 | MMP-13 | Breakdown of ECM | Up-regulated | Remodeling of the extracellular matrix Immune response |
[66] |
| Matrix metalloproteinase 19 | MMP-19 | Breakdown of ECM | Up-regulated | Remodeling of the extracellular matrix Chronic inflammation |
[46] |
| Osteopontin | OPN | Cell adhesion Signal transduction |
Up-regulated | Collagen synthesis Fibroproliferation |
[73] |
| Periostin | POSTN | Tissue development Regeneration |
Up-regulated | Collagen synthesis Proliferation of KFB Migration of KFB Invasion of KFB |
[71] |
| S100 Calcium binding protein | S100 | Cell cycle progression Cell differentiation |
Down-regulated | ECM production | [69] |
| Thymic stromal lymphopoietin | TSLP | Immune response Inflammatory response |
Up-regulated | Increased collagen I and collagen III expression | [58] |
| Inflammatory response | |||||
| Chemokine-like factor 1 | CKLF-1 | Immune surveillance Inflammation response |
Up-regulated | Inflammatory response | [60] |
| C-X-C Motif chemokine receptor 4 | CXCR4 | Regulation of cell migration Inflammatory response |
Up-regulated | Inflammatory response | [59, 60] |
| C-X-C Motif chemokine ligand 9 | CXCL9 | Immunoregulatory Inflammation response |
Up-regulated | Inflammatory response | [61] |
| C-X-C Motif chemokine ligand 12 | CXCL12 | Immune surveillance Inflammation response |
Up-regulated | Activation of the inflammatory response | [62] |
| Interleukin 17 | IL-17 | Proinflammatory cytokine | Positive | Inflammation Fibrosis |
[109, 110] |
| Angiogenesis | |||||
| Interleukin 8 | IL-8 | Chemotactic factor | Up-regulated | Increased recruitment of endothelial progenitor cells | [80] |
| Jagged canonical notch ligand 1 | JAG1 | Fibroblast growth factor-induced angiogenesis | Up-regulated | Angiogenesis Enhanced fibroblast activity |
[83] |
| Vascular endothelial growth factor | VEGF | Angiogenesis Endothelial cell growth |
Positive in the basal layer of the epidermis | Angiogenesis | [85, 86] |
| Platelet-derived growth factor | PDGF | Angiogenesis Cell proliferation Differentiation |
Positive | Angiogenesis Fibronectin production |
[85] |
| Endothelial–mesenchymal transition | |||||
| Interleukin 18 | IL-18 | Proinflammatory cytokine | Up-regulated | Epithelial–mesenchymal interaction Increased collagen expression Increased secretion of profibrotic cytokines |
[98] |
| Phosphatase and tensin homolog deleted on chromosome ten | PTEN | Tumor suppressor | Positive in keloid keratinocytes | EMT transition | [99, 100] |
| Signal transducer and activator of transcription 3 | STAT3 | Cell growth Apoptosis |
Up-regulated | Epithelial–mesenchymal interaction Cell proliferation Collagen production |
[101] |
| Wingless-type MMTV integration site family, member 3A | Wnt3A | Regulation of cell fate Patterning during embryogenesis |
Up-regulated | EMT transition | [102] |
| Stem cells in keloids | |||||
| Kruppel-like factor 4 | KLF4 | Differentiation of epithelial cells | Positive in keloid-derived precursor cells | Development of individualized induced pluripotent stem cells from fibroblasts | [107] |
| Lin-28 homolog | LIN28 | Developmental timing | Positive in keloid-derived precursor cells | Development of individualized induced pluripotent stem cells from fibroblasts | [107] |
| Octamer-binding protein 4 | 4-Oct | Embryonic development Stem cell pluripotency |
Positive in keloid-derived precursor cells | Development of individualized induced pluripotent stem cells from fibroblasts | [107] |
| Sry-box transcription factor 2 | SOX2 | Embryonic development Determination of cell fate |
Positive in keloid-derived precursor cells | Development of individualized induced pluripotent stem cells from fibroblasts | [107] |
KFB keloid fibroblast cells, EMT endothelial–mesenchymal transition, ECM extracellular matrix