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Title: Tacrolimus induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-429 and its target of RhoE

Abstract

Tacrolimus (FK506) has been demonstrated to reduce epidural fibrosis. However, the detailed mechanism of action has not been elucidated. Aberrant miR-429 is involved in many diseases. The aim of this study was to describe the exact mechanism of FK506 induced apoptosis in fibroblasts and the prevention of epidural fibrosis. FK506 induced fibroblast apoptosis was evaluated using CCK-8 assays, flow cytometry, and western blotting. The expression of miR-429 in fibroblasts treated with FK506 was determined by RT-qPCR. Additionally, luciferase activity assays were used to determine the target relationship between miR-429 and RhoE. Flow cytometry and western blot analysis were used to determine the effects of FK506 and miR-429 on fibroblast apoptosis. The effects of FK506 and RhoE on fibroblast apoptosis were determined by CCK-8 assay, flow cytometry, and western blotting. We also evaluate the effects of FK506 and miR-429 on epidural fibrosis in rats by using histological analysis and TUNEL-staining. The results revealed FK506 induces fibroblast apoptosis and significantly downregulates miR-429 expression in fibroblasts. Additionally, miR-429 downregulation caused the apoptosis of fibroblasts. The luciferase activity assay confirmed that RhoE is a direct target of miR-429 and RhoE promotes fibroblast apoptosis. The rat model demonstrated miR-429 inhibition promotes fibroblast apoptosis and epiduralmore » fibrosis, which is consistent with the results of FK506 treatment. Our study demonstrates that FK506 induces fibroblast apoptosis and reduces epidural fibrosis by regulating miR-429 expression and its target of RhoE. - Highlights: • FK506 could inhibit the proliferation and induce the apoptosis of human fibroblast. • FK506 could downregulate the expression of miR-429 and RhoE is a target gene of miR-429. • Inhibits the function of RohE could reduce the apoptosis of human fibroblast after treatment of FK506. • Inhibits the miR-429 function could inhibit proliferation and induce apoptosis of fibroblast and reduce epidural fibrosis.« less

Authors:
; ; ; ; ; ;
Publication Date:
OSTI Identifier:
22719059
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 490; Journal Issue: 4; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL PROLIFERATION; FIBROBLASTS; FIBROSIS; GENES; INHIBITION; LUCIFERASE; RATS

Citation Formats

Li, Xiaolei, Chen, Hui, Wang, Shuguang, Dai, Jihang, Yan, Lianqi, Wang, Jingcheng, and Sun, Yu. Tacrolimus induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-429 and its target of RhoE. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.06.181.
Li, Xiaolei, Chen, Hui, Wang, Shuguang, Dai, Jihang, Yan, Lianqi, Wang, Jingcheng, & Sun, Yu. Tacrolimus induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-429 and its target of RhoE. United States. doi:10.1016/J.BBRC.2017.06.181.
Li, Xiaolei, Chen, Hui, Wang, Shuguang, Dai, Jihang, Yan, Lianqi, Wang, Jingcheng, and Sun, Yu. Sat . "Tacrolimus induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-429 and its target of RhoE". United States. doi:10.1016/J.BBRC.2017.06.181.
@article{osti_22719059,
title = {Tacrolimus induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-429 and its target of RhoE},
author = {Li, Xiaolei and Chen, Hui and Wang, Shuguang and Dai, Jihang and Yan, Lianqi and Wang, Jingcheng and Sun, Yu},
abstractNote = {Tacrolimus (FK506) has been demonstrated to reduce epidural fibrosis. However, the detailed mechanism of action has not been elucidated. Aberrant miR-429 is involved in many diseases. The aim of this study was to describe the exact mechanism of FK506 induced apoptosis in fibroblasts and the prevention of epidural fibrosis. FK506 induced fibroblast apoptosis was evaluated using CCK-8 assays, flow cytometry, and western blotting. The expression of miR-429 in fibroblasts treated with FK506 was determined by RT-qPCR. Additionally, luciferase activity assays were used to determine the target relationship between miR-429 and RhoE. Flow cytometry and western blot analysis were used to determine the effects of FK506 and miR-429 on fibroblast apoptosis. The effects of FK506 and RhoE on fibroblast apoptosis were determined by CCK-8 assay, flow cytometry, and western blotting. We also evaluate the effects of FK506 and miR-429 on epidural fibrosis in rats by using histological analysis and TUNEL-staining. The results revealed FK506 induces fibroblast apoptosis and significantly downregulates miR-429 expression in fibroblasts. Additionally, miR-429 downregulation caused the apoptosis of fibroblasts. The luciferase activity assay confirmed that RhoE is a direct target of miR-429 and RhoE promotes fibroblast apoptosis. The rat model demonstrated miR-429 inhibition promotes fibroblast apoptosis and epidural fibrosis, which is consistent with the results of FK506 treatment. Our study demonstrates that FK506 induces fibroblast apoptosis and reduces epidural fibrosis by regulating miR-429 expression and its target of RhoE. - Highlights: • FK506 could inhibit the proliferation and induce the apoptosis of human fibroblast. • FK506 could downregulate the expression of miR-429 and RhoE is a target gene of miR-429. • Inhibits the function of RohE could reduce the apoptosis of human fibroblast after treatment of FK506. • Inhibits the miR-429 function could inhibit proliferation and induce apoptosis of fibroblast and reduce epidural fibrosis.},
doi = {10.1016/J.BBRC.2017.06.181},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 490,
place = {United States},
year = {2017},
month = {9}
}