Suppressive effects of human fetal keratinocytes on the proliferation, differentiation and extracellular matrix synthesis of human hypertrophic scar fibroblasts in vitro

Abstract

A hypertrophic scar is characterized by fibroblast proliferation and excessive extracellular matrix deposition. Emerging evidence has revealed that fetal keratinocytes (KCs) contribute to scarless wound healing. However, the association between fetal keratinocytes and hypertrophic scarring remains unclear. In the present study, human KCs of different gestational ages were isolated and co-cultured with human hypertrophic scar fibroblasts (HSFbs) or normal skin fibroblasts. Gene expression and protein levels of fibronectin, collagen 1and α-smooth muscle actin in the fibroblasts were measured by reverse transcription-quantitative polymerase chain reaction and western blot analyses. It was observed that fetal KCs significantly inhibited the proliferation of HSFbs in vitro. Fetal keratinocytes also affected the expression of fibronectin, collagen 1 and α-smooth muscle actin in HSFbs. In addition, miR-940 may modulate the suppressive effects of fetal KCs on the cell proliferation, differentiation and extracellular matrix synthesis of HSFbs by directly targeting transforming growth factor-β1. Taken together, the results of the present study provide evidence to support the potential use of fetal KCs for cell-based therapeutic grafting in the prevention of hypertrophic scarring.

Silencing of long noncoding INHBA antisense RNA1 suppresses proliferation, migration, and extracellular matrix deposition in human hypertrophic scar fibroblasts via regulating microRNA-141-3p/myeloid cell leukemia 1 axis

“…Collagen I (Col I), collagen III (Col III), collagen IV (Col IV) and alpha smooth muscle actin (α-SMA) levels are visibly intensified during HS, which together play significant roles in the fibrotic ECM environments [ 6 , 7 ]. Accumulating study confirms that suppression of HSF proliferation, migration and ECM accumulation relieve HS development [ 8 , 9 ]. Long non-coding RNA (lncRNA) is a novel type of noncoding RNAs with limited or no protein-coding ability and over 200 nucleotides in length [ 10 ].…”

The Need for Basic, Translational, and Clinical Research in the Field of Hypertrophic Scars

“…Another paper displayed the importance of K-F crosstalk when studying fetal keratinocytes of differing gestational ages and the effect of their co-culture with fibroblasts on pro-fibrotic proteins. The co-culture of HTS fibroblasts with fetal keratinocytes (fetuses are known to produce scarless healing phenotypes) decreased proliferation of fibroblasts and decreased expression of collagen-1, α-SMA, and fibronectin [27].…”