Background: Transforming growth factor-beta (TGF-β) plays an instrumental role in forming scars and keloids. TGF-β isoforms exhibit differential expression, indicating distinct wound healing and scar formation functions. However, the role of TGF-β1 and TGF-β3 in wound healing and scar formation remains unclear. This study aimed to compare the specific roles of TGF-β1 and TGF-β3 in wound healing and scar formation by biomolecular analysis. Materials and Methods: The study was conducted by cell isolation and culture cells from a total of 20 human samples. Normal human fibroblasts (NHF) were isolated from normal human samples and myofibroblasts from the different scar types, namely hypertrophic (HT) and keloid (K) scars. NHF and cells from the HT, and K scar, each of which were divided into 3 sample groups: the untreated control, TGF-β1 (10 µg/ mL)-treated group, and TGF-β3 (10 µg/mL)-treated group. The results of confocal microscopy and fluorescence-activated cell sorting experiments were compared. Results: Both the HT and K groups had higher α-smooth muscle actin (α-SMA) expression than the NHF group in the untreated control group. In comparison with the untreated group, NHFs showed a significant increase in α-SMA expression in the TGF-β1-treated group. HT showed a high α-SMA level, which was statistically significant compared with the normal fibroblasts. In the TGF-β3-treated group, α-SMA expression was slightly increased in NHF as compared with the untreated group. TGF-β3 treated HT exhibited a greater reduction in α-SMA expression than in the TGF-β1 treated HT. K, on the other hand, had only a minimal effect on the treatment of TGF-β1 and TGF-β3. Conclusions: The findings suggest that TGF-β3 may play a regulatory role in the wound repair process, which could be useful in the development of scar-reducing therapies for patients with scar-related cosmetic concerns.
Cancer-associated fibroblasts (CAFs) are one of the most prevalent cell types within the tumor microenvironment (TME). While several physicochemical cues from the TME, including growth factors, cytokines, and ECM specificity, have been identified as essential factors for CAF activation, the precise mechanism of how the ECM architecture regulates CAF initiation remains elusive. Using a gelatin-based electrospun fiber mesh, we examined the effect of matrix fiber density on CAF activation induced by MCF-7 conditioned media (CM). A less dense (3D) gelatin mesh matrix facilitated better activation of dermal fibroblasts into a CAF-like phenotype in the CM than a highly dense (3D) gelatin mesh matrix. In addition, it was discovered that CAF activation on the less dense (LD) matrix is dependent on the cell size-related AKT/mTOR signaling cascade, accompanied by an increase in intracellular tension within the well-spread fibroblasts.
A scar is considered a natural consequence of the wound-healing process. However, the mechanism by which scars form remains unclear. Here, we suggest a new mechanism of wound healing and scar formation that involves the mechanosensitive regulation of HOX genes. RNA-sequencing of fibroblasts from different types of scars revealed differential HOX gene expression. Computational simulations predicted injury-induced tension loss in the skin, and in vitro experiments revealed a negative correlation between tension and fibroblast proliferation. Remarkably, exogenous tensile stress in fibroblasts has been shown to alter HOX gene expression levels in different scar types. Overall, we propose a model for normal wound healing and scar formation and show that successful wound healing requires tensional homeostasis in the skin tissue, which is regulated by tension-sensitive HOX genes.
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