Table 3.
Keratinocyte–fibroblast crosstalk in fibrotic pathologies.
| References | Pathology | Experimental outcome |
|---|---|---|
| Dufour et al. (13) | SSc | SScF compared to HDF produce higher col-I when exposed to NEK-CM |
| McCoy et al. (16) | SSc | SScK compared to NEK induce higher col-I and αSMA expression by HDF |
| Nikitorowicz-Buniak et al. (24) | SSc | SSc epidermis expresses higher S100A9 compared to dermis and HD epidermis S100A9 enhances HDF and SScF proliferation, migration, and CTGF production |
| Aden et al. (36) | SSc | SSc epidermal explants produce more IL-1α resulting in enhanced gel contraction by HDF |
| Canady et al. (28) | SSc, keloid | SSc and keloid fibroblasts express higher levels of KGF KGF induces keratinocytes to release OSM leading to fibroblast activation |
| Gauglitz et al. (21) | Keloid | Keloid skin expresses lower levels of S100A7 and higher levels of COL1A1, COL1A2, COL3A1 in the dermis than HD. S100A7 decrease HDF production of COL1A1, COL1A2, COL3A1, TGF-β1, TGF-β2, TGF-β3, laminin-β2, α-SMA, and HDF proliferation |
| Do et al. (32) | Keloids | Keloids-K produce more IL-18 than NEK IL-18 enhances col-I, IL-6, IL-8 production by HDF |
| Lim et al. (37) | Keloids | Keloids-K and fibroblasts coculture produce angiogenin, OSM, VEGF, IGF-binding protein-1, OPG, and TGF-β2, and HD coculture does not |
| Funayama et al. (53) | Keloids | Keloid-K enhanced keloid-F proliferation, resistance to apoptosis (upregulation of Bcl-2) and TGF-β1 expression |
| Phan et al. (54) | Keloids | Keloid-K increased proliferation of HD and K-fibroblasts, on an IGFBP-3-dependent mechanism |
| Lim et al. (56) | Keloids | Keloid-K increased col-I and col-III production by HDF |
| Lim et al. (57) | Keloids | Keloids-k induced proliferation of HDF more than NEK |
| Simon et al. (31) | Hypertrophic scars | K from hypertrophic scars increase dermal matrix thickness by enhanced production of TIMP-1. |
| Niessen et al. (58) | Hypertrophic scars | High IL-1α expression at month 3 predicts normal scar; no relationship between IL-1β and TNF expression. High levels of PDGF and bFGF at 12 months correlate with hypertrophic scar |
The references are grouped per pathology. Additional details on culture conditions and mediators are reported in Tables 1, 2. αSMA, alpha-smooth muscle actin; bFGF, basic fibroblast growth factor; Col, collagen; CTGF, connective tissue growth factor; FGF, fibroblast growth factor; HD, healthy donor; HDF, healthy donor fibroblasts; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor binding protein; IL, interleukin; Keloids-F, keloids fibroblasts; Keloids-K, keloids keratinocytes; KGF, keratinocyte growth factor; MMP, metalloproteinase; NEK, healthy donor keratinocytes; OPG, osteoprotegerin; OSM, oncostatin M;PDGF, platelet-derived growth factor; S100A7, psoriasin; S100A8/A9, calprotectin; SSc, Systemic sclerosis; SSc-F, SSc fibroblasts; SSc-K, SSc keratinocytes; TGF, Transforming growth factor; THBS1, Thrombospondin 1; TIMP, tissue inhibitor of metalloproteinases; TNF, Tumor necrosis factor; VEGF, vascular endothelial growth factor.