NOD2 deletion promotes cardiac hypertrophy and fibrosis induced by pressure overload

Zong, Jing; Salim, Mohamed; Zhou, Haoming; Bian, Zhou‐Yan; Dai, Jia; Yuan, Yuan; Deng, Wei; Zhang, Jieyu; Zhang, Rui; Wu, Qin; Tang, Qi‐Zhu

doi:10.1038/labinvest.2013.99

Cited by 31 publications

(19 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be noted that a very recent study showed that NOD2 deletion promotes cardiac hypertrophy and fibrosis induced by pressure overload [36], which differs from our current findings and by others showing the detrimental role of NODs in the regulation of cardiac functions [25,26]. The mixed observation may result from the possible different contribution of NOD2 in different diseased states or different experimental animal models used.…”

Section: Discussioncontrasting

confidence: 99%

NOD2 Deficiency Protects against Cardiac Remodeling after Myocardial Infarction in Mice

Li²,

Chu³

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Although the pathogenesis of myocardial infarction (MI) is multifactorial, activation of innate immune system to induce inflammation has emerged as a key pathophysiological process in MI. NOD2, one member of the NOD-like receptor (NLR) family, plays an important role in the innate immune response. This study was to examine the role of NOD2 during MI. Methods: MI was induced by permanent ligation of the left coronary artery in wild type and NOD2^-/- mice and cardiac fibroblasts were isolated. Results: NOD2 expression was significantly increased in myocardium in post-MI mice. NOD2 deficiency improved cardiac dysfunction and remodeling after MI as evidenced by echocardiographic analysis, reduced the levels of cytokines, inflammatory cell infiltration and matrix metalloproteinase-9 (MMP-9) activity. In vitro, we further found that NOD2 activation induced the activation of MAPK signaling pathways, production of proinflammatory mediators and MMP-9 activity in cardiac fibroblasts. Conclusions: Our studies demonstrate that NOD2 is a critical component of a signal transduction pathway that links cardiac injury by exacerbation of inflammation and MMP-9 activity. Pharmacological targeting of NOD2-mediated signaling pathways may provide a novel approach to treatment of cardiovascular diseases.

show abstract

Section: Discussioncontrasting

confidence: 99%

NOD2 Deficiency Protects against Cardiac Remodeling after Myocardial Infarction in Mice

Li²,

Chu³

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Lrrk2 −/− and Myd88 −/− mice on a C57BL/6J background were from Jax. Nod2 −/− mice (RIKEN), which have been described previously 48 , were originally on a C57BL/6J congenic background and were backcrossed with wild-type C57BL/6J mice for two more generations after arriving in our facility. All SPF mice, including wild-type C57BL/J6, were bred and housed in a barrier facility accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International for SPF mice (Laboratory Animal Facility of Tsinghua University).…”

Section: Methodsmentioning

confidence: 99%

Commensal bacteria direct selective cargo sorting to promote symbiosis

et al. 2015

View full text Add to dashboard Cite

Mucosal immunity protects a host from intestinal inflammation and infection and is profoundly influenced by symbiotic bacteria. Here we report that in mice symbiotic bacteria directed selective cargo sorting in Paneth cells to promote symbiosis through Nod2, a cytosolic bacterial sensor, and the multifunctional protein kinase LRRK2, both encoded by inflammatory bowel disease (IBD)-associated genes. Commensals recruited Nod2 onto lysozyme-containing dense core vesicles (DCVs), which was required for DCV localization of LRRK2 and a small GTPase, Rab2a. Deficiency of Nod2, LRRK2 or Rab2a or depletion of commensals resulted in lysosomal degradation of lysozyme. Thus, commensal bacteria and host factors orchestrate the lysozyme-sorting process to protect the host from enteric infection, implicating Paneth cell dysfunction in IBD pathogenesis.

show abstract

“…MAPK signaling is initiated in cardiac myocytes by various stress stimuli. Once activated, downstream JNKs, p38, and ERKs phosphorylate a wide array of intracellular targets including numerous transcription factors; this results in the reprogramming of cardiac gene expression [19,26,27]. NOD-like receptors (NLRs), the major constituents of the cytosolic innate immunesensing machinery, participate in multiple pathways including NF-κB and MAPK pathways [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…Activation of inflammatory cytokines and NF-κB signaling mediate the development and progression of cardiac hypertrophy [19]. We examined the mRNA expression of NF-κB target genes, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, in the cardiac tissue of KO mice and their WT littermates 8 weeks after AB (Fig.…”

Section: Nlrp1 Ablation Weakens Cardiac Inflammationmentioning

confidence: 99%

Nuclear Localization Leucine-Rich-Repeat Protein 1 Deficiency Protects Against Cardiac Hypertrophy by Pressure Overload

Zong

Liang

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a cytoplasmic protein, involved in autoimmune diseases, mammalian reproduction, neuronal cell death, and stroke. However, the role of NLRP1 in cardiac hypertrophy remains unclear. We used in vivo and in vitro models to investigate the effects of NLRP1 on cardiac hypertrophy. Methods: We used NLRP1-deficient mice and cultured neonatal rat cardiomyocytes with gain and loss of NLRP1 function. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements, and by pathological and molecular analysis. Results: Eight weeks after aortic banding (AB), NLRP1 deficiency significantly inhibited aortic banding–induced cardiac hypertrophy, inflammation, and fibrosis. Activation of MAPK, NF-κB, and TGF-β/Smad pathways was reduced in NLRP1-knockout (KO) mice compared with that in wild-type (WT) mice. Consistent with these results, in vitro studies, performed using cultured neonatal mouse cardiomyocytes, confirmed that NLRP1 deficiency protects against cardiomyocyte hypertrophy induced by isoproterenol (PE); this protective activity was associated with the arrest of MAPK and NF-κB signaling. Conclusions: Our data illustrates that NLRP1 plays a crucial role in the development of cardiac hypertrophy via positive regulation of the MAPK, NF-κB, and TGF-β/Smad signaling pathways.

show abstract

NOD2 deletion promotes cardiac hypertrophy and fibrosis induced by pressure overload

Cited by 31 publications

References 41 publications

NOD2 Deficiency Protects against Cardiac Remodeling after Myocardial Infarction in Mice

NOD2 Deficiency Protects against Cardiac Remodeling after Myocardial Infarction in Mice

Commensal bacteria direct selective cargo sorting to promote symbiosis

Nuclear Localization Leucine-Rich-Repeat Protein 1 Deficiency Protects Against Cardiac Hypertrophy by Pressure Overload

Contact Info

Product

Resources

About