Material Type  

 학위논문

 

0017161695

Date and Time of Latest Transaction  

20250211151431

ISBN  

9798382784311

DDC  

574

Author  

Bigger-Allen, Alexander Andrew.

Title/Author  

Assessment of the Impact of Bromodomain Inhibition on the Actin Cytoskeleton and Contraction.

Publish Info  

[S.l.] : Harvard University., 2024

Publish Info  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Material Info  

178 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-12, Section: B.

General Note  

Advisor: Adam, Rosalyn M.

학위논문주기  

Thesis (Ph.D.)--Harvard University, 2024.

Abstracts/Etc  

요약Injury to contractile organs such as the heart, vasculature, urinary bladder and gut can stimulate a pathological response that results in loss of normal contractility. PDGF and TGFβ are among the most well studied initiators of the injury response and have been shown to induce aberrant contraction in mechanically active cells of hollow organs including smooth muscle cells (SMC) and fibroblasts. However, the mechanisms driving contractile alterations downstream of PDGF and TGFβ in SMC and fibroblasts are incompletely understood, limiting therapeutic interventions. To identify potential molecular targets, we have leveraged the analysis of publicly available data, comparing transcriptomic changes in mechanically active cells stimulated with PDGF and TGFβ and identified a shared molecular profile regulated by MYC and members of the AP-1 transcription factor complex. We also analyzed data sets from SMC and fibroblasts treated in the presence or absence of the MYC inhibitor JQ1. This analysis revealed a unique set of cytoskeleton-associated genes that were sensitive to MYC inhibition. JQ1 was also able to attenuate TGFβ and PDGF induced changes to the cytoskeleton and contraction of smooth muscle cells and fibroblasts in vitro. These findings identify MYC as a key driver of aberrant cytoskeletal and contractile changes in fibroblasts and SMC, and suggest that JQ1 could be used to restore normal contractile function in hollow organs.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Bioinformatics.

Subject Added Entry-Topical Term  

Biochemistry.

Index Term-Uncontrolled  

Contraction

Index Term-Uncontrolled  

Fibroblasts

Index Term-Uncontrolled  

Fibrosis

Index Term-Uncontrolled  

Smooth muscle cells

Index Term-Uncontrolled  

Cytoskeleton

Added Entry-Corporate Name  

Harvard University Medical Sciences

Host Item Entry  

Dissertations Abstracts International. 85-12B.

Electronic Location and Access  

로그인을 한후 보실 수 있는 자료입니다.

Control Number  

joongbu:654052