Tetrandrine induces microRNA differential expression in human hypertrophic scar fibroblasts in vitro

Abstract

ABSTRACT. MicroRNAs (miRNAs) have recently been shown to play a role in normal wound healing process. miRNAs may be linked to pathologic wound healing and closely related to the formation of hypertrophic scars. This study aimed to explore the effects of tetrandrine on the miRNA expression profile in human hypertrophic scar fibroblasts (HSFs) in vitro. HSFs were randomly divided into two groups: the tetrandrine treatment group and the control group. The experimental and control groups were collected and analyzed by miRNA array after a 48-h culture. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to confirm the array results. The targets of differentially expressed miRNA were functionally annotated using bioinformatic approaches. miRNA microarray analysis identified 193 differentially expressed miRNAs and the expression of 186 miRNAs in the experimental group decreased while that of 7 miRNAs increased compared to the control group. The most significantly downregulated miRNA was hsa-miR-1246, and hsa-miR-27b had the highest expression level. Significant differentially expressed miRNAs were predicted to be related to several important signaling pathways related to scar wound healing. The differential miRNA expression identified in this study provides the experimental basis for further understanding the antifibrosis effect of tetrandrine.

Molecular mechanism of myofibroblast formation and strategies for clinical drugs treatments in hypertrophic scars

“…And let7 and miR‐21 could also indirectly influence myofibroblast formation through activating HMGA2 and Smad7, respectively (Cho et al, ). miR‐143‐3p was combination with the 3′‐untranslated region (UTR) of CTGF and miR‐27b with the 3′‐UTR of TGF‐receptor 1, and Smad2, both of which had antifibrosis effects by inhibiting the expression of ECM‐related proteins to prevent the occurrence and development of HTS (Ning et al, ). Besides, miR‐129, miR‐200b/c, and miR‐216a have been reported which promoted the expression of fibrous genes in mouse glomerular mesangial cells (Azevedo‐Pouly et al, ; Cheng et al, ; Chiang et al, ; Du et al, ).…”

A critical review: traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji)

“…However, this study lacked use of a positive control. Tetrandrine (8.0 lM) also exerted an antifibrotic effect on human hypertrophic scar fibroblasts by inducing the expression of microRNA, transforming growth factor-b1 (TGF-b1), SMAD family member 2 (Smad2) and SMAD family member 7 (Smad7) (Ning et al 2016). Tetrandrine (4.0-20.0 lM) could inhibit human hypertrophic scar fibroblasts at least partially through induction of Smad7 and decrement of Smad2 resulting in inhibition of TGF-b1 transcription and its intracellular signaling, which led to reduction of type I and III collagen production and suppression of cell reproductive activity (Li et al 2012).…”

Bioactive Ingredients in Chinese Herbal Medicines That Target Non-coding RNAs: Promising New Choices for Disease Treatment

“…The underlying mechanism was suggested to be repression of DNA and collagen synthesis in scar-derived fibroblasts (Liu et al, 2001). Furthermore, by upregulating miR-27b and downregulating miR-125b, TET influenced the expression of putative targets, including VEGFC, BCL2L12, COL4A3, and FGFR2, predicted to contribute to several scar and wound healing-related signaling pathways (Ning et al, 2016). Consequently, TET has therapeutic potential for the inhibition of skin tissue hyperplasia after wounding or surgery.…”