Swainsonine inhibits proliferation and collagen synthesis of NIH-3T3 cells by declining miR-21.
Swainsonine (SW) is an indolizidine alkaloid first discovered in Swainsona canescens. This study explored the effects of SW on mouse embryo fibroblast NIH-3T3 cell proliferation and collagen synthesis, as well as potential molecule mechanisms. We discovered that SW exposure lowered the viability and proliferation of NIH-3T3 cells. The collagen synthesis was reduced after SW exposure, as evidenced by declines of the mRNA and protein levels of collagen I (CoI I), collagen III (CoI III) and α-smooth muscle actin (α-SMA) in NIH-3T3 cells, as well as reduction of collagen concentration in the culture supernatant of NIH-3T3 cells. Mechanically, transforming growth factor β1 (TGF-β1) stimulation elevated the microRNA-21 (miR-21) expression in NIH-3T3 cells. SW reversed the TGF-β1-caused elevation of miR-21. Up-regulation of miR-21 attenuated the inhibitory influences of SW on NIH-3T3 cell viability, proliferation and collagen synthesis. Silence of miR-21 had converse influence. Besides, SW inactivated PI3K/AKT and NF-κB pathways via declining miR-21. Altogether, SW inhibited the proliferation and collagen synthesis of fibroblast NIH-3T3 might be through declining miR-21 and then suppressing PI3K/AKT and NF-κB pathways. SW may be an effective therapeutic medicine for scar hyperplasia.
['Li|Chao|C|', 'Wang|Peipei|P|', 'Fu|Ziyang|Z|', 'Li|Yongtao|Y|', 'Li|Shouju|S|']
D000818:Animals D001483:Base Sequence D049109:Cell Proliferation D003094:Collagen D005347:Fibroblasts D005786:Gene Expression Regulation D051379:Mice D035683:MicroRNAs D016328:NF-kappa B D041681:NIH 3T3 Cells D019869:Phosphatidylinositol 3-Kinases D051057:Proto-Oncogene Proteins c-akt D017026:Swainsonine D053773:Transforming Growth Factor beta1
Swainsonine fibroblasts microRNA-21 NF-κB pathway Scar hyperplasia PI3K/AKT pathway