Effect of Hypertrophic Scar Fibroblast-Derived Exosomes on Keratinocytes of Normal Human Skin

Abstract

Epidermal keratinocytes are highly activated, hyper-proliferated, and abnormally differentiated in the post-burn hypertrophic scar (HTS); however, the effects of scar fibroblasts (SFs) on keratinocytes through cell–cell interaction in HTS remain unknown. Here, we investigated the effects of HTSF-derived exosomes on the proliferation and differentiation of normal human keratinocytes (NHKs) compared with normal fibroblasts (NFs) and their possible mechanism to provide a reference for clinical intervention of HTS. Fibroblasts were isolated and cultured from HTS and normal skin. Both HTSF-exosomes and NF-exosomes were extracted via a column-based method from the cell culture supernatant. NHKs were treated for 24 or 48 h with 100 μg/mL of cell-derived exosomes. The expression of proliferation markers (Ki-67 and keratin 14), activation markers (keratins 6, 16, and 17), differentiation markers (keratins 1 and 10), apoptosis factors (Bax, Bcl2, caspase 14, and ASK1), proliferation/differentiation regulators (p21 and p27), and epithelial–mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and vimentin) was investigated. Compared with NF-exosomes, HTSF-exosomes altered the molecular pattern of proliferation, activation, differentiation, and apoptosis, proliferation/differentiation regulators of NHKs, and EMT markers differently. In conclusion, our findings indicate that HTSF-derived exosomes may play a role in the epidermal pathological development of HTS.

Design, Synthesis, and Biological Evaluation of an Orally Bioavailable, Potent, and Selective ROCK2 Inhibitor for Psoriasis Treatment

“…Furthermore, we assessed the protein expressions of matrix metalloproteinase-2 (MMP-2), fibronectin (FN), N-cadherin, and elastin in KGF-induced HaCaT cells. These proteins are known to be epithelial–mesenchymal transition (EMT) markers and highly expressed in psoriasis patients. − Notably, the treatment of A31 resulted in a significant reduction in the expression levels of all four proteins in KGF-induced HaCaT cells (Figure ). This observation indicates that A31 can effectively inhibit the expression of these key proteins involved in psoriasis pathogenesis.…”

Exosomes: The emerging mechanisms and potential clinical applications in dermatology

“…This suggested that HSF-derived exosomes can modulate the behavior of normal fibroblasts and promote the production of ECM components. In another research, HHSFs-derived exosomes promoted the proliferation, migration, and EMT and differentiation marker KRT1 and KRT10 expression of normal human keratinocytes (NHK) 123 . In the context of keloids, miR-21 expression was significantly higher in exosomes from keloid fibroblasts (KFs) compared to that in normal fibroblasts 124 .…”

Hydrogel Loaded with Components for Therapeutic Applications in Hypertrophic Scars and Keloids

“… 42 Hypertrophic scar fibroblast-derived exosomes upregulated the EMT markers of keratinocytes. 43 Moreover, increased WNT5A promotes interleukin-6-dependent EMT in keloid keratinocytes by regulating the JAK/STAT pathway. 44 It was reported that pirfenidone, an antifibrotic drug, could reduce the EMT-like phenotype in keloid keratinocytes.…”