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Assessment of the Impact of Bromodomain Inhibition on the Actin Cytoskeleton and Contraction
Assessment of the Impact of Bromodomain Inhibition on the Actin Cytoskeleton and Contraction
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151431
- ISBN
- 9798382784311
- DDC
- 574
- 서명/저자
- Assessment of the Impact of Bromodomain Inhibition on the Actin Cytoskeleton and Contraction
- 발행사항
- [Sl] : Harvard University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 178 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Adam, Rosalyn M.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2024.
- 초록/해제
- 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.
- 일반주제명
- Cellular biology
- 일반주제명
- Bioinformatics
- 일반주제명
- Biochemistry
- 키워드
- Contraction
- 키워드
- Fibroblasts
- 키워드
- Fibrosis
- 키워드
- Cytoskeleton
- 기타저자
- Harvard University Medical Sciences
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798382784311
■035 ▼a(MiAaPQ)AAI31295378
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aBigger-Allen, Alexander Andrew.▼0(orcid)0000-0001-6914-9135
■24510▼aAssessment of the Impact of Bromodomain Inhibition on the Actin Cytoskeleton and Contraction
■260 ▼a[Sl]▼bHarvard University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a178 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Adam, Rosalyn M.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2024.
■520 ▼aInjury 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.
■590 ▼aSchool code: 0084.
■650 4▼aCellular biology
■650 4▼aBioinformatics
■650 4▼aBiochemistry
■653 ▼aContraction
■653 ▼aFibroblasts
■653 ▼aFibrosis
■653 ▼aSmooth muscle cells
■653 ▼aCytoskeleton
■690 ▼a0379
■690 ▼a0715
■690 ▼a0487
■71020▼aHarvard University▼bMedical Sciences.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161695▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
