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Calponin 1 inhibits agonist-induced ERK activation and decreases calcium sensitization in vascular smooth muscle

Lova Prasadareddy Kajuluri1, Qing Rex Lyu2,3, Jaser Doja2

  • 1Vascular Biology Laboratory, Department of Health Sciences, Boston University, Boston, Massachusetts, USA.

Journal of Cellular and Molecular Medicine
|December 26, 2023
PubMed

Insights

Calponin 1 (CNN1) is crucial for smooth muscle cell (SMC) contraction. Ablating CNN1 in mice alters SMC tone maintenance and stress, impacting vascular tone regulation.

Area of Science:

  • Vascular Biology
  • Cellular Physiology
  • Molecular Mechanisms

Background:

  • Smooth muscle cell (SMC) contraction and vascular tone are complex processes.
  • Extracellular regulated kinase (ERK) and its signaling pathways are implicated in SMC function.
  • Calponin 1 (CNN1) has been suggested to scaffold signaling proteins like protein kinase C (PKC) and ERK.

Purpose of the Study:

  • To investigate the role of Calponin 1 (CNN1) in ERK activation and SMC contractility in mice.
  • To generate and utilize a novel Calponin 1 knockout (Cnn1 KO) mouse model with preferential vascular SMC expression changes.

Main Methods:

  • Generation of a Calponin 1 knockout (Cnn1 KO) mouse model via a specific intronic CArG box mutation.
  • Analysis of SMC stress, stiffness, ERK activation, and smooth muscle (SM) tone maintenance in Cnn1 KO mice under varying calcium conditions and agonist stimulation.

Main Results:

  • Ablation of CNN1 led to reduced stress and stiffness amplitude with increased ERK activation during elevated intracellular calcium.
  • In conditions of intracellular calcium depletion with agonist presence, Cnn1 KO mice showed prolonged SM tone maintenance.
  • These findings highlight context-dependent effects of CNN1 on SMC contractile properties.

Conclusions:

  • CNN1 plays a significant and multifaceted role in modulating the amplitude and maintenance of SMC contractile tone.
  • The study provides new insights into the regulatory mechanisms of vascular tone and SMC function.
  • The Cnn1 KO mouse model is a valuable tool for studying CNN1's function in vascular physiology.
Keywords:
CRISPRERKarterial stiffnesscalcium sensitizationcalponinsmooth muscle

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