![]() ![]() ![]() Seki reported that the fake receptor of transforming growth factor-beta (TGF- β), bone morphogenetic protein, and activin membrane-bound inhibitor (BAMBI) could be downregulated by stimulating the TLR4 on the membrane of hepatic stellate cells, which further activates the TGF- β1 signal pathway and contributes to the liver fibrosis. Multiple internal and external substances, such as taxol, fibulin, hyaluronic acid, oligosaccharide, HSP60, HSP70, fibrinogen, and High-mobility group box 1 (HMGB1), can be recognized by TLR4, making TLR4 a promising target in the field of antivirus, antibacteria, and tissue repairment. It includes lipopolysaccharide (LPS), bacterial lipoprotein, CpG DNA, virus double-strain RNA, hyaluronic acid, heat shock protein (HSPs), and S100 protein. Toll-like receptors (TLRs) are a couple of transmembrane proteins located on the cytomembrane, which recognize the conservative pathogen-associated molecular patterns (PAMPs). It attracted our interest in its potential role and mechanism in the development and process of HTS. lncRNA PAPPA-AS1 is a rarely studied lncRNA which was only discussed in adenovirus infection, placenta percreta, and osteoporosis, with very limited information in its properties. In our preliminary experiment, we found that lncRNA PAPPA-AS1 was differentially expressed in the HTS tissues and normal skin tissues based on the bioinformatics analysis. Accumulative evidences suggested the significant function of lncRNA in the process and development of HTS and fibrosis. However, in recent years, lncRNAs are reported to be involved in multiple cellular biological processes, such as epigenetic, transcriptional, and posttranscriptional regulation of gene expression, the silence of X chromosome, the activation of transcription, and nuclear transmission. lncRNAs are noncoding RNAs greater than 200 nucleotides in length, which are originally regarded as the “noise” in the genome transcription without biological functions. It is of great significance to explore the possible molecular mechanism underlying HTS for the clinical treatment of HTS.Įpigenetics is a biological research method investigating the changes in phenotype that are not rooted in DNA sequence, including the DNA methylation, histone modification, chromatin remodeling, and noncoding RNA. Although multiple hypotheses have been proposed to claim the pathogenesis of HTS, the pathological mechanism of HTS still remains unknown. ![]() The pathological characteristics of HTS are the abnormal proliferation of fibroblasts, the transformation of fibroblasts to myofibroblasts, and the excessive accumulation of the extracellular matrix (ECM). Not only the normal physiological function and appearance but also the psychology of the patients are significantly influenced by HTS, which contributes to the impaired social interaction and is generally considered as a public health issue. Hypertrophic scar (HTS) is the complication of burns or wounds, which is mainly clinically characterized with local redness, itchy pain, hyperplasia becoming hard, local contracture, articular dyskinesia, and even repeated rupturing or cancerization. In conclusion, lncRNA PAPPA-AS1 might induce the development of HTS by upregulating TLR4 through interacting with TAF15. Positive correlation and interaction were observed between PAPPA-AS1 and TAF15 and between TAF15 and the promoter of TLR4, respectively. It was accompanied by the alleviated pathological state in the HTS tissues, which were significantly reversed by cotransfecting with the pcDNA3.1-TLR4 vector. By knocking down PAPPA-AS1, the proliferation of HTsFb cells, TLR4, and TGF- β1 signal pathway and the expression of fibrosis markers both in HTsFb cells and HTS tissues were suppressed. The expression levels of TLR4, MyD88, TGF- β1, collagen I, collagen III, and α-SMA were greatly elevated in HTsFb cells. PAPPA-AS1 was significantly upregulated in both HTS tissues and hypertrophic scar fibroblast (HTsFb) cells. Bioinformatics analysis was utilized to screen the differentially expressed lncRNAs in HTS tissues. In the present study, the regulatory effect of lncRNA PAPPA-AS1 on the Toll-like receptor 4 (TLR4) signal pathway, as well as the molecular mechanism, was investigated. PAPPA-AS1, a differentially expressed long noncoding RNA (lncRNA) in the HTS tissues, attracted our interests in its potential role and mechanism in the development and process of HTS. Hypertrophic scar (HTS) is a complicated pathological process induced mainly by burns and wounds, with abnormal proliferation of fibroblasts and the transformation of fibroblasts to myofibroblasts. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |