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. 2021 Nov 30;9(12):1802. doi: 10.3390/biomedicines9121802

Table 1.

Overview of the biological functions of the examined target genes.

Grouping Target Gene Biological Function
Inflammatory cytokines IL1A
  • -

    keratinocytes and fibroblasts secrete a broad spectrum of cytokines including IL-1α, IL-6, and IL-8 [34,35];

  • -

    the IL-1 cytokine family plays a crucial role through alerting the body to immediate dangers and initiating the inflammatory cascade in the skin as well as inducing gene expression and synthesis of other inflammatory mediators [45,46];

  • -

    the initial inflammatory response after injury is essential for wound healing and stimulates regenerative processes [41];

  • -

    promotion of the acute inflammation can increase wound healing [39,47]; and

  • -

    reduction in IL-6 by anti-inflammatory treatment has been shown to inhibit scratch wound healing [48].
IL6
CXCL8
Growth factors TGFB1
  • -

    keratinocytes and fibroblasts secrete a broad spectrum of growth factors including TGF-β and PDGF [34,35];

  • -

    TGF-β plays an important role in wound healing (stimulating granulation tissue formation [49,50,51,52], mediating fibroblast proliferation as well as collagen production, ECM deposition and myofibroblast differentiation [53,54,55]);

  • -

    TGF-β promotes angiogenesis [1];

  • -

    increased TGF-β activity can accelerate wound healing [56,57];

  • -

    induction of TGFB1 has been associated with promotion of keratinocyte proliferation and migration [58]; and

  • -

    PDGF-C is a key component of the PDGFR-α signaling pathway and possesses similar modulation capacity of fibroblast differentiation as TGF-β [59].
PDGFC
Transcription factors NFKB1
  • -

    NF-κB transcription factors have been implicated in the regulation of several genes: apoptosis, immune response and inflammatory processes [60,61,62];

  • -

    NF-κB is a major regulator of cell proliferation and migration acting as transcription factor for both, cyclin D and MMP-9 [63];

  • -

    NF-κB is essential for wound healing [64];

  • -

    p53 (gene TP53) regulates cell cycle progression after DNA damage, activation of DNA repair mechanisms and cell apoptosis, if DNA damage proves to be irreparable [64]; and

  • -

    expression of TP53 and NFKB is elevated during wound healing [63,64].
TP53
Heat shock proteins HSP90AA1
  • -

    HSPs have crucial roles in protein folding and as possible signaling regulators inducing cellular stress responses [65,66,67];

  • -

    constitute a large group of chaperone proteins found in virtually all organisms, where they modulate cellular homeostasis, aid in repair after cellular stress and promote wound healing [47];

  • -

    classified into several families on the basis of their molecular size and amino acid sequence similarity with highly differentiated expression patterns, intracellular localization and function [68];

  • -

    induced under conditions of cell stress, e.g., inflammation [68];

  • -

    HSP90 is an abundant cellular protein constituting about 1–2% of total protein in non-stressed cells and about 4–6% in stressed tissues [69,70];

  • -

    HSP90 assists proper protein folding and prevents aggregation of non-native proteins [71];

  • -

    HSPA1 (previously designated HSP70) is another cytoprotective agent with very low transcript levels in unstressed normal cells;

  • -

    HSPA1 plays a crucial role in guiding conformational status of the proteins during folding and translocation [72] and conferring thermo-resistance [73];

  • -

    HSPD1 (previously HSP60) is foremost located as a chaperonin in the cytosol and mitochondrial matrix [74];

  • -

    HSPD1 induces an inflammatory response through several different receptors including TLR2, TLR4 and CD36 [65,67]; and

  • -

    HSDP1 has been implicated in wound healing [75].
HSPA1A
HSPD1
Antimicrobial peptides DEFB1
  • -

    keratinocytes can produce a wide variety of AMPs upon stimulation [34,76];

  • -

    AMPs are important effector molecules with broad spectrum anti-microbial activity against bacteria, fungi and even viruses [77,78,79,80,81];

  • -

    endogenous AMPs are upregulated in all stages of wound healing in vivo indicating a role beyond microbial defense toward regulation of immune response, granulation tissue formation and re-epithelization [82,83];

  • -

    insufficient upregulation of defensins in chronic wounds such as diabetic foot and venous leg ulcers has been suggested to contribute to the chronicity of ulcers by reduced antimicrobial defense [84,85]; and

  • -

    an increased TH2 cytokine expression contributes to the reduction in AMPs observed in atopic dermatitis resulting in frequent skin infections [86,87].
RNASE7
S100A7
Structural components DSG1
  • -

    keratinocytes form a tight cell barrier by connecting neighboring cells to each other through intercellular junctions, which include (corneo) desmosomes, adherens junctions and tight junctions [88]; and

  • -

    desmosomes are composed of the desmosomal cadherins such as desmogleins (Dsg) 1–4 and desmocollins 1–3, which are transmembrane glycoproteins of the cadherin superfamily [89].
DSG3
COL1A1
  • -

    collagen, type I, alpha 1, also known as alpha-1 type I collagen;

  • -

    is the major component of type I collagen, the fibrillar collagen found in most connective tissues including cartilage;

  • -

    type III collagen is found in the skin, lungs, intestinal walls, and the walls of blood vessels; and

  • -

    components of type III collagen, called pro-α1(III) chains, are produced from the COL3A1 gene.
COL1A3