Apromising method to target the transforming growth factor receptor I (TGFβRI) – also known as activin-like kinase 5 (ALK5), is by making use of exon skipping through antisense oligonucleotides. In hypertrophic scarring (HTS) the distinguishing border between the papillary dermis and reticular dermis is completely abrogated, thus, exhibiting a one layered dermis containing a heterogenous fibroblast population—comprising papillary fibroblasts (PFs), reticular fibroblasts (RFs) and myofibroblasts(MFs). 

A new study published in Burns investigated the effect of TGFβRI inhibition by exon skipping in PF, RF and HTS fibroblast monocultures. 

Morphological analyses revealed the presence of a PF-like population after exon skipping in the different fibroblast cultures. This observation was further confirmed by the expression of genes specific for PFs. In addition, investigations on mRNA and protein level revealed that and to a lesser extent RFs are targeted by exon skipping. Furthermore, collagen gel contraction analysis showed that ALK5 exon skipping reduced TGF-β- induced contraction together with decreased alpha-smooth muscle actin expression levels. 

Thus, the results demonstrated that exon skipping primarily targets pro-fibrotic fibroblasts. This could be a promising step towards the prevention of HTS development in burn tissue.

Source: Burns. 2021 Jan 23;S0305-4179(21)00011-5. doi: 10.1016/j.burns.2021.01.004.