Endogenous peptide LYENRL prevents the activation of hypertrophic scar-derived fibroblasts by inhibiting the TGF-beta 1/Smad pathway
LIFE SCIENCES
Authors: Ji, Xiaojun; Tang, Zhe; Shuai, Weiwei; Zhang, Zhirui; Li, Jingyun; Chen, Ling; Cao, Jing; Yin, Wu
Abstract
Hypertrophic scar formation is a fibroproliferative disorder caused by abnormal wound healing. At present, there are limited treatment strategies for hypertrophic scars. In this study, we identified an endogenous peptide, LYENRL, through peptidomics screening that is downregulated in scar skin tissues. The peptide exhibited concentration dependent inhibitory effects on the proliferation, migration and extracellular matrix (ECM) production of scar fibroblasts. By eukaryotic transcriptome sequencing analysis, we noted that LYENRL downregulated gene sets in scar fibroblasts were associated with the transforming growth factor-beta (TGF-beta) signaling pathway. Further experiments revealed that LYENRL was able to inhibit the activation of TGF-beta 1/Smad signaling and TGF-beta 1-induced activation of scar fibroblasts at the source by blocking the binding of AP-1 to the corresponding region of the Tgfb1 promoter, which in turn inhibited gene expression of Tgfb1. Taken together, we concluded that the effects of LYENRL on scar fibroblasts make it a potential peptide drug for hypertrophic scar treatment.
HK3 overexpression associated with epithelial-mesenchymal transition in colorectal cancer
BMC GENOMICS
Authors: Pudova, Elena A.; Kudryavtseva, Anna V.; Fedorova, Maria S.; Zaretsky, Andrew R.; Shcherbo, Dmitry S.; Lukyanova, Elena N.; Popov, Anatoly Y.; Sadritdinova, Asiya F.; Abramov, Ivan S.; Kharitonov, Sergey L.; Krasnov, George S.; Klimina, Kseniya M.; Koroban, Nadezhda V.; Volchenko, Nadezhda N.; Nyushko, Kirill M.; Melnikova, Nataliya V.; Chernichenko, Maria A.; Sidorov, Dmitry V.; Alekseev, Boris Y.; Kiseleva, Marina V.; Kaprin, Andrey D.; Dmitriev, Alexey A.; Snezhkina, Anastasiya V.
Abstract
Background: Colorectal cancer (CRC) is a common cancer worldwide. The main cause of death in CRC includes tumor progression and metastasis. At molecular level, these processes may be triggered by epithelial-mesenchymal transition (EMT) and necessitates specific alterations in cell metabolism. Although several EMT-related metabolic changes have been described in CRC, the mechanism is still poorly understood. Results: Using CrossHub software, we analyzed RNA-Seq expression profile data of CRC derived from The Cancer Genome Atlas (TCGA) project. Correlation analysis between the change in the expression of genes involved in glycolysis and EMT was performed. We obtained the set of genes with significant correlation coefficients, which included 21 EMT-related genes and a single glycolytic gene, HK3. The mRNA level of these genes was measured in 78 paired colorectal cancer samples by quantitative polymerase chain reaction (qPCR). Upregulation of HK3 and deregulation of 11 genes (COL1A1, TWIST1, NFATC1, GLIPR2, SFPR1, FLNA, GREM1, SFRP2, ZEB2, SPP1, and RARRES1) involved in EMT were found. The results of correlation study showed that the expression of HK3 demonstrated a strong correlation with 7 of the 21 examined genes (ZEB2, GREM1, TGFB3, TGFB1, SNAI2, TWIST1, and COL1A1) in CRC. Conclusions: Upregulation of HK3 is associated with EMT in CRC and may be a crucial metabolic adaptation for rapid proliferation, survival, and metastases of CRC cells.
COA
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