AMF siRNA treatment of keloid through inhibition signaling pathway of RhoA/ROCK1

Tian, Yuan; Jin, Lihua; Zhang, Wenhong; Zu-meng, YA; Cheng, Yuan; Zhao, Hongyun

doi:10.1016/j.gendis.2018.05.002

Cited by 7 publications

(2 citation statements)

References 32 publications

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“…RNA interference is a universal mechanism of post-transcriptional gene silencing induced by siRNAs, which are double-stranded non-coding RNAs of 21–22 nucleotides in length generated from longer double strand RNA by the action of Dicer ( 49 ). siRNA is able to prevent target gene expression by inducing the degradation of specific mRNA ( 50 ). In the present study, Runx2 siRNA was designed to knockdown Runx2 mRNA and transfected into HKFs.…”

Section: Discussionmentioning

confidence: 99%

Treatment of keloids through Runx2 siRNA‑induced inhibition of the PI3K/AKT signaling pathway

Ren

et al. 2020

Mol Med Rep

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Keloids are a skin fibroproliferative condition characterized by the hyperproliferation of fibroblasts and the excessive deposition of extracellular matrix (ECM) components. Previous studies have determined that Caveolin-1 controlled hyperresponsiveness to mechanical stimuli through Runt-related transcription factor 2 (Runx2) activation in keloids. However, the molecular mechanism of Runx2 regulating the pathological progression of keloids has not been elucidated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that most of the differentially expressed genes (DEGs), including Runx2, were significantly enriched in the biological processes ‘Positive regulation of cell proliferation’, in the cellular components ‘Extracellular matrix’, in the molecular functions ‘Extracellular matrix structural constituents’ and in the KEGG ‘PI3K-Akt signaling pathway’. The aim of the present study was to investigate the expression levels of the Runx2 in human keloid tissues and primary human keloid fibroblasts (HKFs), and to determine the underlying molecular mechanisms involved in the fibrotic roles of Runx2 in keloid formation. Runx2 expression levels were analyzed in patient keloid tissues and HKFs using western blotting, reverse transcription-quantitative PCR (RT-qPCR) and immunofluorescence microscopy. Primary HKFs were transfected with a small interfering RNA (si) specifically targeting Runx2 (si-Runx2). Subsequently, Cell Counting Kit-8, wound healing and Transwell assays, flow cytometry, RT-qPCR and western blotting were applied to evaluate the proliferation, migration, apoptosis, ECM deposition and PI3K/AKT signaling pathway of HKFs, respectively. In addition, western blotting was also used to determine the expression levels of phosphorylated AKT and PI3K in HKFs. The results revealed that Runx2 expression levels were upregulated in keloid tissues and primary HKFs compared with the normal skin tissues and human normal fibroblasts. Following the transfection with si-Runx2, the proliferative and migratory abilities of HKFs were significantly reduced and the apoptotic rate was increased. The expression levels of type I, type III collagen, fibronectin, and α-smooth muscle actin were downregulated in si-Runx2-transfected cells, which was hypothesized to occur through following the downregulation of the phosphorylation levels of PI3K and AKT. In conclusion, the findings of the present study indicated that Runx2 silencing in HKFs might significantly inhibit the cell proliferation, migration and the expression levels of ECM-related proteins, and promote apoptosis via suppressing the PI3K/AKT signaling pathway. Thus, Runx2 siRNA treatment may reverse the pathological phenotype of keloids through the inhibition of PI3K/AKT signaling in patients.

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Section: Discussionmentioning

confidence: 99%

Treatment of keloids through Runx2 siRNA‑induced inhibition of the PI3K/AKT signaling pathway

Ren

et al. 2020

Mol Med Rep

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“…Tissue specimens from keloids and foreskin (normal skin used as control [25][26][27][28] ) were cut under aseptic conditions, and epithelial and subcutaneous tissues were removed carefully with ophthalmic scissors. The specimens were washed three times with D-Hanks' solution and sheared into tissue pieces of 1 mm 3 .…”

Section: Separation and Culture Of Fibroblast Cellsmentioning

confidence: 99%

MicroRNA-21 may be involved in the therapeutic effects of Galla chinensis ointment on keloid

et al. 2020

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Objective: Galla chinensis ointment can inhibit the proliferation of keloid fibroblasts and decrease keloid formation. We investigated whether Galla chinensis ointment inhibits keloid fibroblast proliferation through expression of microRNA-21, phosphorylated (p)-phosphatidylinositol 3-kinase (p-PI3K), chromosome 10 neutropenic protein phosphatase (PTEN), protein kinase B (p-Akt), and mammalian target of rapamycin (p-mTOR). Methods: A keloid mouse model and human keloid-derived fibroblasts were developed and treated with Galla chinensis. Immunohistochemistry, western blot, and reverse transcription-PCR were used to detect miR-21, PI3K, PTEN, Akt, and mTOR in keloid tissues. Results: p-Akt and p-mTOR were highly expressed in the control group, PTEN was highly expressed in the treatment group, and p-PI3K was highly expressed in keloid tissue in both groups. Galla chinensis reduced miR-21 expression and increased PTEN mRNA expression in keloid fibroblasts compared with the control group, resulting in increased PTEN protein and decreased p-Akt and p-mTOR protein. Galla chinensis had no effect on p-PI3K. Conclusion: Galla chinensis might inhibit proliferation of keloid fibroblasts by upregulating PTEN, thus inhibiting expression of miR-21 and downregulating p-Akt and p-mTOR expression. These results confirm the effect of Galla chinensis ointment on fibroblasts and suggest that it could be used to manage keloids clinically.

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Identifying miRNA modules associated with progression of keloids through weighted gene co-expression network analysis and experimental validation in vitro

Ren

et al. 2021

Burns

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AMF siRNA treatment of keloid through inhibition signaling pathway of RhoA/ROCK1

Cited by 7 publications

References 32 publications

Treatment of keloids through Runx2 siRNA‑induced inhibition of the PI3K/AKT signaling pathway

Treatment of keloids through Runx2 siRNA‑induced inhibition of the PI3K/AKT signaling pathway

MicroRNA-21 may be involved in the therapeutic effects of Galla chinensis ointment on keloid

Identifying miRNA modules associated with progression of keloids through weighted gene co-expression network analysis and experimental validation in vitro

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