2. Academic Validation
  3. NKRF in Cardiac Fibroblasts Protects against Cardiac Remodeling Post-Myocardial Infarction via Human Antigen R

NKRF in Cardiac Fibroblasts Protects against Cardiac Remodeling Post-Myocardial Infarction via Human Antigen R

  • Adv Sci (Weinh). 2023 Sep 5;e2303283. doi: 10.1002/advs.202303283.
Chenghu Guo 1,  Wei Ji 2,  Wei Yang 1,  Qiming Deng 1,  Tengfei Zheng 1,  Zunzhe Wang 3,  Wenhai Sui 1,  Chungang Zhai 1,  Fangpu Yu 1,  Bo Xi 4,  Xiao Yu 5,  Feng Xu 6,  Qunye Zhang 1,  Wencheng Zhang 1,  Jing Kong 1,  Meng Zhang 1 7,  Cheng Zhang 1 7
Affiliations

Affiliations

  • 1 National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, 250012, China.
  • 2 Department of Ultrasonography, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.
  • 3 Department of Geriatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
  • 4 Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
  • 5 Key Laboratory Experimental Teratology of the Ministry of Education, Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
  • 6 Department of Emergency Medicine, Chest Pain Center, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, 250012, China.
  • 7 Cardiovascular Disease Research Center of Shandong First Medical University, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, China.
PMID: 37667861 DOI: 10.1002/advs.202303283
Abstract

Myocardial infarction (MI) remains the leading cause of death worldwide. Cardiac fibroblasts (CFs) are abundant in the heart and are responsible for cardiac repair post-MI. NF-κB-repressing factor (NKRF) plays a significant role in the transcriptional inhibition of various specific genes. However, the NKRF action mechanism in CFs remains unclear in cardiac repair post-MI. This study investigates the NKRF mechanism in cardiac remodeling and dysfunction post-MI by establishing a CF-specific NKRF-knockout (NKRF-CKO) mouse model. NKRF expression is downregulated in CFs in response to pathological cardiac remodeling in vivo and TNF-α in vitro. NKRF-CKO mice demonstrate worse cardiac function and survival and increased infarct size, heart weight, and MMP2 and MMP9 expression post-MI compared with littermates. NKRF inhibits CF migration and invasion in vitro by downregulating MMP2 and MMP9 expression. Mechanistically, NKRF inhibits human antigen R (HuR) transcription by binding to the classical negative regulatory element within the HuR promoter via an NF-κB-dependent mechanism. This decreases HuR-targeted Mmp2 and Mmp9 mRNA stability. This study suggests that NKRF is a therapeutic target for pathological cardiac remodeling.

Keywords

NF-κB-repressing factor; cardiac fibroblasts; human antigen R; myocardial infarction; transcriptional and post-transcriptional regulation.

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