Exploring Skin Wound Healing Models and the Impact of Natural Lipids on the Healing Process.

Cutaneous wound healing is a complex biological process involving a series of well-coordinated events aimed at restoring skin integrity and function. Various experimental models have been developed to study the mechanisms underlying skin wound repair and to evaluate potential therapeutic interventions. This review explores the diverse array of skin wound healing models utilized in research, ranging from rodent excisional wounds to advanced tissue engineering constructs and microfluidic platforms. More importantly, the influence of lipids on the wound healing process is examined, emphasizing their role in enhancing barrier function restoration, modulating inflammation, promoting cell proliferation, and promoting remodeling. Lipids, such as phospholipids, sphingolipids, and ceramides, play crucial roles in membrane structure, cell signaling, and tissue repair. Understanding the interplay between lipids and the wound microenvironment provides valuable insights into the development of novel therapeutic strategies for promoting efficient wound healing and tissue regeneration. This review highlights the significance of investigating skin wound healing models and elucidating the intricate involvement of lipids in the healing process, offering potential avenues for improving clinical outcomes in wound management.

Loss of Indoleamine-2,3-Dioxygenase-1 (IDO1) in Knockout Mice Does Not Affect the Development of Skin Lesions in the Imiquimod-Induced Mouse Model of Psoriasis.

Indoleamine-2,3-dioxygenase (IDO) degrades the essential amino acid tryptophan resulting in tryptophan depletion and the accumulation of catabolites such as kynurenine. The expression/activity of IDO in various cells, including macrophages and dendritic cells, results in an inhibition of T-cell responses in a number of situations, such as toward allogeneic fetuses and tissue grafts. Psoriasis is an immune-mediated skin disease involving T cells; kynureninase and its generation of catabolites downstream of IDO are reported to play an important role in this disease. We hypothesized that mice lacking the IDO1 gene would exhibit a hyperactive immune response and an exacerbation of skin lesions in the imiquimod-induced mouse model of psoriasis. Littermate wild-type and IDO1-knockout mice were treated with imiquimod for 5 days, and the severity of psoriasiform skin lesions assessed using the psoriasis area and severity index (PASI), ear edema measured using a digital caliper, and thickness of the epidermis determined by histology. Expression of pro-inflammatory mediators and tryptophan-metabolizing enzymes was monitored using quantitative RT-PCR. Imiquimod increased ear edema, PASI scores, and epidermal thickness in both WT and IDO1 knockout mice; however, there were no differences observed between the 2 genotypes. There were also no differences in imiquimod's induction of skin inflammatory mediators, indicating no effect of IDO1 gene loss in this psoriasis model. Although these data suggest a lack of involvement of IDO1 in psoriatic skin inflammation, other possible mechanisms, such as compensatory changes in other pathways and the involvement of the IDO2 isoform, must also be considered.

TGFß- and bleomycin-induced extracellular matrix synthesis is mediated through Akt and mammalian target of rapamycin (mTOR).

A number of pro-fibrogenic stimuli, such as growth factors, cytokines, and extracellular matrix (ECM) proteins, involve Akt and its downstream substrates in mediating their effects. We previously reported that absence of Akt1, which is the predominant isoform of the three gene Akt family in vascular cells, resulted in impaired ECM remodeling in skin and vasculature. In the current study, we investigated the importance of Akt1 in TGFß- and bleomycin-induced synthesis and secretion of ECM proteins by fibroblasts. We observed that both TGFß and bleomycin stimulated the synthesis of ECM proteins in a dose- and time-dependent manner. Treatment with TGFß and bleomycin also resulted in increased phosphorylation of Akt, mammalian target of rapamycin (mTOR) and their downstream signaling partners, p70S6 Kinase, Ribosomal S6 protein and 4E-BP1, resulting in the activation of this pathway. The effects of TGFß and bleomycin on ECM synthesis were blunted by pre-treatment with an mTOR inhibitor rapamycin. Whereas mTOR is responsible for the transcriptional regulation of a number of ECM proteins, adhesion molecules and matrix metalloproteases (MMPs), synthesis of major ECM proteins such as fibronectin and collagens (types I, II and V) by fibroblasts in response to TGFß and bleomycin is regulated by mTOR at the translational level. These findings indicate the importance of the Akt-mTOR signaling pathway in TGF-mediated fibrogenic events in vivo.