Roles of the HIF-1α pathway in the development and progression of keloids.

Keloids, a pathological scar that is induced by the consequence of aberrant wound healing, is still a major global health concern for its unsatisfactory treatment outcomes. HIF-1α, a main regulator of hypoxia, mainly acts through some proteins or signaling pathways and plays important roles in a variety of biological processes. Accumulating evidence has shown that HIF-1α played a crucial role in the process of keloid formation. In this review, we attempted to summarize the current knowledge on the association between HIF-1α expression and the development and progression of keloids. Through a comprehensive analysis, the molecular mechanisms underlying HIF-1α in keloids were shown to be correlated to the proliferation of fibroblasts, angiogenesis, and collagen deposits. The affected proteins and the signaling pathways were multiple. For instance, HIF-1α was reported to promote keloids formation by enhancing angiogenesis, fibroblast proliferation, and collagen deposition through the activation of periostin PI3K/Akt, TGF-ß/Smad and TLR4/MyD88/NF-κB pathway. However, the specific effects of HIF-1α on keloids keloid illnesses in clinical practice is are entirely unclear, and further studies in clinical trials are still warranted. Therefore, an in-depth understanding of the biological mechanisms of HIF-1α in keloid formation is significant to develop promising therapeutic targets for the treatment of keloids in clinical practice.

Roles of MicroRNA-21 in Skin Wound Healing: A Comprehensive Review.

MicroRNA-21 (miR-21), one of the early mammalian miRNAs identified, has been detected to be upregulated in multiple biological processes. Increasing evidence has demonstrated the potential values of miR-21 in cutaneous damage and skin wound healing, but lack of a review article to summarize the current evidence on this issue. Based on this review, relevant studies demonstrated that miR-21 played an essential role in wound healing by constituting a complex network with its targeted genes (i.e., PTEN, RECK. SPRY1/2, NF-κB, and TIMP3) and the cascaded signaling pathways (i.e., MAPK/ERK, PI3K/Akt, Wnt/ß-catenin/MMP-7, and TGF-ß/Smad7-Smad2/3). The treatment effectiveness developed by miR-21 might be associated with the promotion of the fibroblast differentiation, the improvement of angiogenesis, anti-inflammatory, enhancement of the collagen synthesis, and the re-epithelialization of the wound. Currently, miRNA nanocarrier systems have been developed, supporting the feasibility clinical feasibility of such miR-21-based therapy. After further investigations, miR-21 may serve as a potential therapeutic target for wound healing.

microRNA-98 mediated microvascular hyperpermeability during burn shock phase via inhibiting FIH-1.

BACKGROUND: microRNA is a small non-coding RNA molecule and functions in RNA silencing and post-transcriptional regulation of gene expression. This study was designed to evaluate the role of miR-98 in the development of microvascular permeability and its molecular pathogenesis. METHODS: Forty-eight healthy adult Wistar rats were divided into the control group (n = 8) and burn group (n = 40) that inflicted with 30% total body surface area third-degree burn. Groups were processed at 2, 4, 8, 12, and 24 h post-burn. Plasma for vascular endothelial cell culture was collected from control and 12 h post-burn rats. Organic microvascular permeability and serum miR-98 level were measured. In vitro, rat aorta endothelial cells were stimulated with burn serum. Level of miR-98 and protein of hypoxia-inducible factor-1 (HIF-1), factor inhibiting HIF-1α (FIH-1), and tight junction-associated proteins were determined. RESULTS: Organic microvascular permeability began to rise at 2 h post-burn and maintained the same character throughout the experiment except in lung tissue that was still rising at 12 h; the serum level of miR-98 was elevated (P < 0.05). In vitro, burn serum stimulation increased rat aorta endothelial monolayer cell permeability as well as upregulated miR-98 expression (P < 0.05). As shown in the result of transfection experiment, miR-98 negatively regulated FIH-1 and tight junction-associated protein expression (P < 0.05). CONCLUSIONS: The findings of the present study suggest severe microvascular permeability due to burns; and the underlying mechanism bases on the promotion of miR-98 level to the extent that it activated HIF-1 gene expression, resulting in junction-associated protein deficiency.