BROWSE

Related Scientist

Researcher

황대희
식물 노화·수명 연구단
more info

Integration of proteomic and transcriptomic profiles identifies a novel PDGF-MYC network in human smooth muscle cells

Cited 10 time in webofscience Cited 0 time in scopus
479 Viewed 1,096 Downloaded
Title
Integration of proteomic and transcriptomic profiles identifies a novel PDGF-MYC network in human smooth muscle cells
Author(s)
Yang, W; Ramachandran, A; You, S; Jeong, H; Morley, S; Mulone, MD; Logvinenko, T; Kim, J; Daehee Hwang; Freeman, MR; Adam, RM
Publication Date
2014-08
Journal
CELL COMMUNICATION AND SIGNALING, v.12, no.1, pp.44 -
Publisher
BIOMED CENTRAL LTD
Abstract
Background: Platelet-derived growth factor-BB (PDGF-BB) has been implicated in the proliferation, migration and synthetic activities of smooth muscle cells that characterize physiologic and pathologic tissue remodeling in hollow organs. However, neither the molecular basis of PDGFR-regulated signaling webs, nor the extent to which specific components within these networks could be exploited for therapeutic benefit has been fully elucidated. Results: Expression profiling and quantitative proteomics analysis of PDGF-treated primary human bladder smooth muscle cells identified 1,695 genes and 241 proteins as differentially expressed versus non-treated cells. Analysis of gene expression data revealed MYC, JUN, EGR1, MYB, RUNX1, as the transcription factors most significantly networked with up-regulated genes. Forty targets were significantly altered at both the mRNA and protein levels. Proliferation, migration and angiogenesis were the biological processes most significantly associated with this signature, and MYC was the most highly networked master regulator. Alterations in master regulators and gene targets were validated in PDGF-stimulated smooth muscle cells in vitro and in a model of bladder injury in vivo. Pharmacologic inhibition of MYC and JUN confirmed their role in SMC proliferation and migration. Network analysis identified the diaphanous-related formin 3 as a novel PDGF target regulated by MYC and JUN, which was necessary for PDGF-stimulated lamellipodium formation. Conclusions: These findings provide the first systems-level analysis of the PDGF-regulated transcriptome and proteome in normal smooth muscle cells. The analyses revealed an extensive cohort of PDGF-dependent biological processes and connected key transcriptional effectors to their regulation, significantly expanding current knowledge of PDGF-stimulated signaling cascades. These observations also implicate MYC as a novel target for pharmacological intervention in fibroproliferative expansion of smooth muscle, and potentially in cancers in which PDGFR-dependent signaling or MYC activation promote tumor progression.
URI
http://pr.ibs.re.kr/handle/8788114/784
DOI
10.1186/s12964-014-0044-z
ISSN
1478-811X
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > Journal Papers (저널논문)
Files in This Item:
Integration of proteomic and transcriptomic profiles identifies and novel PDGF-MYC network in human smooth muscle cells.pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse