Thymosin beta-4 regulates activation of hepatic stellate cells viahedgehog signaling

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486262.do
DOI
10.1038/s41598-017-03782-x
Title
Thymosin beta-4 regulates activation of hepatic stellate cells viahedgehog signaling
Description
This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korean government (MEST) (No.2014M2B2A9030333).
abstract
The molecular mechanisms of thymosin beta-4 (TB4) involved in regulating hepatic stellate cell (HSC) functions remain unclear. Therefore, we hypothesize that TB4 influences HSC activation through hedgehog (Hh) pathway. HSC functions declined in a TB4 siRNA-treated LX-2. TB4 suppression down-regulated both integrin linked kinase ( ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2. A TB4 CRISPR also blocked the activation of primary HSCs, with decreased expression of smoothened, GLI2 and ILK compared with cells transfected with nontargeting control CRISPR. Double immunostaining and an immunoprecipitation assay revealed that TB4 interacted with either smoothened at the cytoplasm or GLI2 at the nucleus in LX-2. Smoothened suppression in primary HSCs using a Hh antagonist or adenovirus transduction decreased TB4 expression with the reduced activation of HSCs. Tb4-overexpressing transgenic mice treated with CCl4 were susceptible to the development hepatic fibrosis with higher levels of ILK, pGSK3b, and Hh activity, as compared with wild-type mice. These findings demonstrate that TB4 regulates HSC activation by influencing the activity of Smoothened and GLI2, suggesting TB4 as a novel therapeutic target in liver disease.
provenance
Made available in Cube on 2018-09-28T16:02:53Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Jieun
Hyun, Jeongeun
Wang, Sihyung
Lee, Chanbin
Lee, Jae-Wook
Moon, Eun-Yi
Cha, Heejae
Diehl, Anna Mae
Jung, Youngmi
accessioned
2018-09-28T16:02:53Z
available
2018-09-28T16:02:53Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486262.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274174
Jurisdiction
Rep.of Korea
Project Name
Epigenetic regulation of transcriptional signal pathway
rights
openAccess
type
article


Files in This Item

There are no attached files.