MicroRNA‐411‐3p inhibits bleomycin‐induced skin fibrosis by regulating transforming growth factor‐β/Smad ubiquitin regulatory factor‐2 signalling

ACS Appl. Mater. Interfaces

et al. 2022

The skin is the first line of defense for the human body and is vulnerable to injury. Various topical or systemic diseases facilitate skin inflammation, and when the intensity or duration of skin injury exceeds the ability of tissue repair, fibrosis, an outcome of a dysregulated tissue-repair response, begins to dominate the repair process. However, existing methods for reducing skin fibrosis are insufficient and cause side effects, highlighting the need for drugs that effectively inhibit skin fibrosis and reduce immunogenicity, inflammation, apoptosis, and pyroptosis. Tetrahedral framework nucleic acids (tFNAs) are DNA nanomaterials that have a unique spatial structure, demonstrate excellent biosecurity, and promote anti-inflammatory, antioxidative, antifibrotic, angiogenic, and skin-wound-healing activities with almost no toxicity. Here, we explored the potential of tFNAs in skin fibrosis therapy in vitro and in vivo. After incubating cells or injecting mice with profibrogenic molecules and tFNAs, we found that the tFNAs inhibited the epithelial−mesenchymal transition, reduced inflammatory factor levels, decreased skin collagen content, and inhibited the pyroptosis pathway. These findings suggest the potential of tFNAs in treating pyroptosis-related diseases.

Section: Resultsmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 95%

Tetrahedral Framework Nucleic Acids Inhibit Skin Fibrosis via the Pyroptosis Pathway

Jiang

ACS Appl. Mater. Interfaces

et al. 2022

“…This outcome differed from the presentation of rosacea-like lesions induced by short-term LL-37 administration [ 32 ] but was similar to what we have seen in previous studies employing intradermal injections of LL-37 every 24 h for 20 days [ 33 ]. In addition, in studies on bleomycin-induced skin fibrosis, collagen deposition was found to be accompanied by the thickening of both the dermis and epidermis, as well as the upregulation of α-smooth muscle actin and wave protein expression levels [ 34 , 35 ]. In our constructed mouse rosacea model, in addition to the inflammatory manifestations, the above manifestations of skin fibrosis also appeared, which indicates that the rosacea progressed from inflammation to skin fibrosis and further indicates that it is feasible to construct a model of advanced rosacea fibrosis by prolonging the duration and frequency of LL-37 intradermal injections.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Administration of LL-37 Can Induce Irreversible Rosacea-like Lesion

Kang

et al. 2023

CIMB

Self Cite

Rosacea is a chronic inflammatory skin disease whose late manifestations have not yet been clearly reported in animal models. The objective of this study is to describe the skin lesions and major histopathological changes in a rosacea-like phenotype in mice induced by prolonged LL-37 administration and furthermore, to assess the potential of long-term LL-37 administration in inducing irreversible rosacea-like skin lesion models. Balb/c mice were continuously injected intradermally with LL-37 every 12 h to induce a rosacea-like phenotype. After LL-37 injections were administered for 20 consecutive days, the area of rosacea-like lesions gradually expanded in the first 13 days, then entered a stable phase. Haematoxylin and eosin (H&E) and Van Gieson’s staining showed a high degree of inflammatory cell aggregation, thickening of the epidermis and dermis, and collagen deposition in large quantities. The results of immunofluorescence staining and Western blotting showed that the expression of α-SMA, TNF-α, vimentin, and COL1 in the skin of mice was significantly upregulated. Short-term LL-37 administration induced rosacea-like lesions that only featured the aggregation of inflammatory factors and thickening of the epidermis, whereas no collagen hyperplasia was observed, and a full recovery was noticed. However, rosacea-like skin lesions induced by long-term LL-37 administration did not completely recover. Our study compares rosacea-like lesions induced by short-term versus long-term LL-37 administration, and the results suggest that irreversible rosacea-like lesions can be induced by long-term LL-37 administration.

“…In addition to the inflammatory role of some miRNAs, other candidates have been involved in fibrosis or proliferation. For instance, miR-411-3p has been shown to alleviate pulmonary and skin fibrosis through modulation of TGF-β/Smad ubiquitin regulatory factor 2 (Smurf 2) signaling, whereas miR-491-5p inhibits the non-small cell lung cancer (NSCLC) cell proliferation and migration by targeting forkhead box P4 (FOXP4), a transcription factor involved in the regulation of various cancers [42][43][44]. However, the implication of the remaining seven novel miRNAs (miR-7061-5p, 381-3p, miR-7224-3p, 3097-5p, miR-6540-5p, 33-3p, and 1943-5p) in lung biology still unknown.…”

Section: Discussionmentioning

confidence: 99%

Gene network analysis for identification of microRNA biomarkers for asthma

Cay

Singer

2022

Respir Res

Background To date, reliable biomarkers for asthma have not been identified. MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate post-transcriptional gene expression, and they are involved in various diseases, including asthma. MiRNAs may serve as ideal biomarkers due to their ability to regulate multiple pathways. This study aims to identify miRNA biomarker signatures for asthma. Methods We used the house dust mite (HDM) mouse model of allergic inflammation. Mice were phenotyped by assessing lung function, allergic response, airway inflammation, and remodeling. The miRNA signature profiles in serum and lung tissue were determined by small RNA sequencing, and data were analyzed using Qiagen CLC Genomics Workbench. To identify relevant gene targets, we performed mRNA sequencing, followed by miRNA-targets analysis. These miRNAs and targets were subject to subsequent pathway and functional analyses. Results Mice exposed to HDM developed phenotypic features of allergic asthma. miRNA sequencing analysis showed that 213 miRNAs were substantially dysregulated (FDR p-value < 0.05 and fold change expression > + 1.5 and < − 1.5) in the lung of HDM mice relative to the control mice. In contrast, only one miRNA (miR-146b-5p) was significantly increased in serum. Target analysis of lung dysregulated miRNAs revealed a total of 131 miRNAs targeting 211 mRNAs. Pathway analysis showed T helper 2/1 (Th2/Th1) as the top significantly activated signaling pathway associated with the dysregulated miRNAs. The top enriched diseases were inflammatory response and disease, which included asthma. Asthma network analysis indicated that 113 of 131 miRNAs were directly associated with asthma pathogenesis. Conclusions These findings suggest that most dysregulated miRNAs in the HDM model were associated with asthma pathogenesis via Th2 signaling. We identified a panel of 30 miRNAs as potential biomarker candidates for asthma.