These results indicated that miR-21 was a critical regulator for HS formation and TGF- β1/miR-21/Smad7 pathway could be a useful therapeutic target for the treatment of HS.
Preclinical Study of Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Hypertrophic Scars in a Common Marmoset Primate Model.
Alteration in cell morphology triggers transforming growth factor-beta 1, collagenase, and tissue inhibitor of metalloproteinases-I expression in normal and hypertrophic scar fibroblasts.
The present study demonstrated that mast cells and chymase are present in hypertrophic scars, and chymase promotes hypertrophic scar fibroblast proliferation and collagen synthesis by activating the TGF-β1/Smads signaling pathway.
Herein, we present a TGF-β1-inhibitor-doped poly(ε-caprolactone) (PCL)/gelatin (PG) coelectrospun nanofibrous scaffold (PGT) for HS prevention during wound healing.
The transforming growth factor β1 (TGF-β1) promotes fibroblasts proliferation, the synthesis of collagen and other extracellular matrix, and ultimately leads to the formation of the HS by inducing excessive deposition of ECM.
In conclusion, hypertrophic scar tissue and fibroblasts produce more mRNA and protein for transforming growth factor-beta1, which may be important in hypertrophic scar formation.
After finding increased levels of mir-181b in deep dermal fibroblasts, it was demonstrated that TGF-β1 stimulation decreased miR-24 but increased miR-181b and that hypertrophic scar and deep dermis contained increased levels of miR-181b.
Finally, a skin HS model was established in rats and the scar formation was compared between rats treated with vehicle (saline), TGF-β1, and TGF-β1 + TSP-4 shRNA.
Here, we attempted to rationally derive peptide inhibitors from the complex interface of TGF-β1 with TβRII to disrupt such interaction for the suppression of fibroblast activation involved in HS.
Taken together, our data suggest that miR-29b treatment has an inhibitory effect against scar formation via inhibition of the TGF-β1/Smad/CTGF signaling pathway and may provide a potential molecular basis for future treatments for hypertrophic scars.
This study provided evidence that suppression of CTGF could be a viable strategy for hypertrophic scar reduction therapy and that further study of the antisense oligonucleotide EXC 001 was indicated.
Activation of peroxisome proliferator-activated receptor-gamma inhibits transforming growth factor-beta1 induction of connective tissue growth factor and extracellular matrix in hypertrophic scar fibroblasts in vitro.
Elevations of TGF-β3, SMAD2 and SMAD4 in hypertrophic scars and increase of IGF-1R in immature stages may give some clues for acne hypertrophic scar formation.
Normal skin fibroblasts (NSFs) and hypertrophic scar fibroblasts (HSFs) were allowed to infiltrate and proliferate in GAM; at the meantime they were transfected with TMCC/pSUPER-SMAD2 polyplexes to display remarkably reduced SMAD2 levels that lasted for up to 10 days, consequently inhibiting the over-production of type I and type III collagen.
Furthermore, we found that miR-21 was involved in lncRNA COL1A2-AS1-induced expression of Smad7, by which COL1A2-AS1 acted as endogenous sponge to adsorb miR-21 and in turn regulated Smad7 and a cascade of molecular to play a protective role in hypertrophic scar.
These results indicated that the miR‑21 antagomir has a therapeutic effect on HS and suggests that targeting miRNAs may be a successful and novel therapeutic strategy in the treatment of fibrotic diseases that are difficult to treat with existing methods.