Proteomic Identification of ADAM12 as a Regulator for TGF-beta 1-InducedDifferentiation of Human Mesenchymal Stem Cells to Smooth Muscle Cells

Collection with item attached
2012
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/483743.do
DOI
10.1371/journal.pone.0040820
Title
Proteomic Identification of ADAM12 as a Regulator for TGF-beta 1-InducedDifferentiation of Human Mesenchymal Stem Cells to Smooth Muscle Cells
Description
This research was supported by National Research Foundation of Korea(NRF) programs funded by the Ministry of Education, Science, andTechnology (2010-0020274, 2010-0014876), and by the Medical ResearchCenter program (2011-0006193). The funders had no role in study design,data collection and analysis, decision to publish, or preparation of themanuscript.
abstract
Background: Transforming growth factor-beta 1 (TGF-beta 1) induces the differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle cells. Lipid rafts are cholesterol-rich microdomains in cell membranes that reportedly play a key role in receptor-mediated signal transduction and cellular responses. In order to clarify whether lipid rafts are involved in TGF-beta 1-induced differentiation of hASCs into smooth muscle cells, we analyzed the lipid raft proteome of hASCs.
Methods and Results: Pretreatment of hASCs with the lipid raft disruptor methyl-beta-cyclodextrin abrogated TGF-beta 1-induced expression of alpha-smooth muscle actin, a smooth muscle cell marker, suggesting a pivotal role of lipid rafts in TGF-beta 1-induced differentiation of hASCs to smooth muscle cells. Sucrose density gradient centrifugation along with a shotgun proteomic strategy using liquid chromatography-tandem mass spectrometry identified 1002 individual proteins as the lipid raft proteome, and 242 of these were induced by TGF-beta 1 treatment. ADAM12, a disintegrin and metalloproteases family member, was identified as the most highly up-regulated protein in response to TGF-beta 1 treatment. TGF-beta 1 treatment of hASCs stimulated the production of both ADAM12 protein and mRNA. Silencing of endogenous ADAM12 expression using lentiviral small hairpin RNA or small interfering RNA abrogated the TGF-beta 1-induced differentiation of hASCs into smooth muscle cells.
Conclusions: These results suggest a pivotal role for lipid raft-associated ADAM12 in the TGF-beta 1-induced differentiation of hASCs into smooth muscle cells.
provenance
Made available in Cube on 2018-09-28T14:55:00Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Young Mi
Kim, Jaeyoon
Heo, Soon Chul
Shin, Sang Hun
Do, Eun Kyoung
Suh, Dong-Soo
Kim, Ki-Hyung
Yoon, Man-Soo
Lee, Taehoon G.
Kim, Jae Ho
accessioned
2018-09-28T14:55:00Z
available
2018-09-28T14:55:00Z
issued
2012
citation
PLOS ONE(7): 7
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/483743.do
Funder
교육과학기술부
Funding Program
2단계연구중심대학육성(0.5)
Project ID
1345196629
Jurisdiction
Rep.of Korea
Project Name
Pusan National University BK21 Medical science Education Center
rights
openAccess
type
article


Files in This Item

There are no attached files.