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Isolation and Cryopreservation of Neonatal Rat Cardiomyocytes
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Isolation and Cryopreservation of Neonatal Rat Cardiomyocytes

Published on: April 9, 2015

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Molecular network, pathway, and functional analysis of time-dependent gene changes related to cathepsin G exposure in

Sanket Kumar Shukla1, Kunal Sikder1, Amrita Sarkar1

  • 1Department of Medicine, Center of Translational Medicine, Thomas Jefferson University, Philadelphia PA-19107, USA.

Gene
|June 3, 2018
PubMed

Insights

Cathepsin G (CG) exposure triggers time-dependent gene expression changes in neonatal rat cardiomyocytes (NRCMs), leading to myocyte apoptosis. These findings reveal potential therapeutic targets for heart failure.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genomics

Background:

  • The molecular mechanisms underlying cardiomyocyte death following cathepsin G (CG) exposure are not fully understood.
  • Investigating these pathways is crucial for understanding heart failure pathogenesis.

Purpose of the Study:

  • To determine time-dependent gene expression changes in neonatal rat cardiomyocytes (NRCMs) after CG exposure.
  • To identify molecular pathways and potential therapeutic targets involved in CG-induced myocyte apoptosis.

Main Methods:

  • Neonatal rat cardiomyocytes (NRCMs) were exposed to CG over time (1, 4, and 8 hours).
  • Microarray analysis was performed to identify differentially expressed genes.
  • Ingenuity Pathway Analysis (IPA) was used to map overlapped genes and identify signaling pathways.

Main Results:

  • Significant numbers of differentially expressed genes were identified at each time point (451, 572, and 1127).
  • Key up-regulated genes include Hamp, SMAD6, NR4A1, FOSL2, ID3, and SLAMF7.
  • Down-regulated genes include CYR61, GDF6, Olr640, Vom2r36, DUSP6, and MMP20.
  • Deregulation of JAK/Stat, IL-9, and Nur77 signaling pathways was observed.
  • Molecular network analysis revealed connections to ERK1/2, caspase, BCR, and Cyclins.

Conclusions:

  • CG exposure induces time-dependent alterations in gene expression in NRCMs.
  • Multiple signaling pathways are implicated in CG-mediated cardiomyocyte apoptosis.
  • Identified genes and pathways may serve as future therapeutic targets for preserving myocyte survival in heart failure.
Keywords:
ApoptosisCardiomyocyteCathepsin GIPA analysisMicroarray

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