NLRC3 deficiency promotes cutaneous wound healing due to the inhibition of p53 signaling

Qin, Yuan; Wu, Kai; Zhang, Zheng; Pan, Rulu; Lin, Ziqi; Zhang, Wenyi; Huang, Shishun; Dai, Juji; Huang, Ren; Gong, Siqing; Lin, Huan; Chong, Shuyi; Lu, Lijuan; Lu, Xincheng

doi:10.1016/j.bbadis.2022.166518

Cited by 10 publications

(11 citation statements)

References 50 publications

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“…Delayed re-epithelialization and impaired angiogenesis are crucial factors contributing to the complexity of healing DUs. 40 Our results revealed that MRGs, including GLDC and KLK6 may affect DUs by mediating angiogenesis and re-epithelization. GLDC is a pivotal enzyme in the glycine lysis system, whose expression is downregulated in gastric cancer cell lines and tissues, and the proliferation and migration of gastric cancer cells can be inhibited by methylation of GLDC (Min et al, 2016); 41 KLK6 is a secreted serine protease that downregulates mRNA expression in gliomas and can inhibit tumor growth (Lou et al, 2014).…”

Section: Discussionmentioning

confidence: 59%

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Metabolism‐related biomarkers, molecular classification, and immune infiltration in diabetic ulcers with validation

Zhang

Jiang

et al. 2023

International Wound Journal

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Diabetes mellitus (DM) can lead to diabetic ulcers (DUs), which are the most severe complications. Due to the need for more accurate patient classifications and diagnostic models, treatment and management strategies for DU patients still need improvement. The difficulty of diabetic wound healing is caused closely related to biological metabolism and immune chemotaxis reaction dysfunction. Therefore, the purpose of our study is to identify metabolic biomarkers in patients with DU and construct a molecular subtype‐specific prognostic model that is highly accurate and robust. RNA‐sequencing data for DU samples were obtained from the Gene Expression Omnibus (GEO) database. DU patients and normal individuals were compared regarding the expression of metabolism‐related genes (MRGs). Then, a novel diagnostic model based on MRGs was constructed with the random forest algorithm, and classification performance was evaluated utilizing receiver operating characteristic (ROC) analysis. The biological functions of MRGs‐based subtypes were investigated using consensus clustering analysis. A principal component analysis (PCA) was conducted to determine whether MRGs could distinguish between subtypes. We also examined the correlation between MRGs and immune infiltration. Lastly, qRT‐PCR was utilized to validate the expression of the hub MRGs with clinical validations and animal experimentations. Firstly, 8 metabolism‐related hub genes were obtained by random forest algorithm, which could distinguish the DUs from normal samples validated by the ROC curves. Secondly, DU samples could be consensus clustered into three molecular classifications by MRGs, verified by PCA analysis. Thirdly, associations between MRGs and immune infiltration were confirmed, with LYN and Type 1 helper cell significantly positively correlated; RHOH and TGF‐β family remarkably negatively correlated. Finally, clinical validations and animal experiments of DU skin tissue samples showed that the expressions of metabolic hub genes in the DU groups were considerably upregulated, including GLDC, GALNT6, RHOH, XDH, MMP12, KLK6, LYN, and CFB. The current study proposed an auxiliary MRGs‐based DUs model while proposing MRGs‐based molecular clustering and confirmed the association with immune infiltration, facilitating the diagnosis and management of DU patients and designing individualized treatment plans.

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Section: Discussionmentioning

confidence: 59%

“…Similarly, proliferation is also essential to wound healing. Delayed re‐epithelialization and impaired angiogenesis are crucial factors contributing to the complexity of healing DUs 40 . Our results revealed that MRGs, including GLDC and KLK6 may affect DUs by mediating angiogenesis and re‐epithelization.…”

Section: Discussionmentioning

confidence: 70%

Metabolism‐related biomarkers, molecular classification, and immune infiltration in diabetic ulcers with validation

Zhang

Jiang

et al. 2023

International Wound Journal

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“… 53 Furthermore, NLRC3 deficiency promotes cutaneous wound healing due to the inhibition of p53 signaling. 54 As p53 is also involved in vascular remodeling and atherosclerosis, 55 thus we speculate that NLRC3 alteration could have reversed the expression and phosphorylation of p53 that is usually observed in advanced atherosclerotic plaques 56 and therefore reduced restenosis susceptibility. Further studies are needed to explore this relationship.…”

Section: Discussionmentioning

confidence: 88%

Genetic Variants in PHACTR1 & LPL Mediate Restenosis Risk in Coronary Artery Patients

Hageh¹,

Chacar²,

Venkatachalam³

et al. 2023

VHRM

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Background and Objective Coronary artery disease (CAD) is a major cause of death worldwide. Revascularization via stent placement or coronary artery bypass grafting (CABG) are standard treatments for CAD. Despite a high success rate, these approaches are associated with long-term failure due to restenosis. Risk factors associated with restenosis were investigated using a case-control association study design. Methods Five thousand two hundred and forty-two patients were enrolled in this study and were assigned as follows: Stenosis Group: 3570 patients with CAD >50% without a prior stent or CABG (1394 genotyped), and Restenosis Group: 1672 patients with CAD >50% and prior stent deployment or CABG (705 genotyped). Binomial regression models were applied to investigate the association of restenosis with diabetes, hypertension, and dyslipidemia. The genetic association with restenosis was conducted using PLINK 1.9. Results Dyslipidemia is a major risk factor (Odds Ratio (OR) = 2.14, P-value <0.0001) for restenosis particularly among men (OR = 2.32, P < 0.0001), while type 2 diabetes (T2D) was associated with an increased risk of restenosis in women (OR = 1.36, P = 0.01). The rs9349379 ( PHACTR1) and rs264 ( LPL ) were associated with an increased risk of restenosis in our patients. PHACTR1 variant was associated with increased risk of restenosis mainly in women and in diabetic patients, while the LPL variant was associated with increased risk of restenosis in men. Conclusion The rs9349379 in PHACTR1 gene is significantly associated with restenosis, this association is more pronounced in women and in diabetic patients. The rs264 in LPL gene was associated with increased risk of restenosis in male patients.

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“…Ubiquitination of P53 is an important way to regulate this protein ( 30 ). NLRC3 associates with HSP90(Heat Shock Protein 90), preventing the interaction between HSP90, MDM2 and P53, further inhibiting the ubiquitin and degradation of P53 ( 31 ) ( Figure 2E ).…”

Section: Roles Of Nlrc3: From the Molecular Biological Perspectivementioning

confidence: 99%

“…And the initial inflammatory phase and the following proliferative phase are closely related to the outcome of cutaneous wound healing ( 69 ). NLRC3 prevents the inflammation and proliferation during cutaneous wound healing, NLRC3 interacts with Hsp90, inhibits the ubiquitin of P53, further promotes the inhibition on inflammation and cell proliferation by P53 signal pathway ( 31 ) and prevents cutaneous wound healing.…”

Section: Role Of Nlrc3 In Immune-related Diseasesmentioning

confidence: 99%

Negative regulator NLRC3: Its potential role and regulatory mechanism in immune response and immune-related diseases

Sun

Zhang

et al. 2022

Front. Immunol.

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NLRC3 is a member of the pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) family, and plays a pivotal regulatory role in modulating the activation of immune cells. In macrophages, NLRC3 inhibits the activation of the NF-κB signaling pathway, the STING/TBK1 signaling pathway, and the formation of the inflammasome. In the context of T cells immune response, NLRC3 prevents the activation of T cells by regulating the function of dendritic cells and directly influencing the function of T cells. Different from other pattern recognition receptors, NLRC3 is more closely associated with regulatory activity than pathogens recognition, it influences the fates of cells, for example, prevents proliferation, promotes apoptosis and inhibits pyroptosis. These cellular functions regulated by NLRC3 are involved in the development processes of a variety of diseases, such as infectious disease, sterile inflammatory diseases, and cancer. However, its characteristics, function and regulatory mechanism in immune response and immune-related diseases have not been addressed fully. In this review, we elaborate the potential roles of NLRC3 from several different levels, include molecular mechanism, cellular functions in the immune-related diseases.

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NLRC3 deficiency promotes cutaneous wound healing due to the inhibition of p53 signaling

Cited by 10 publications

References 50 publications

Metabolism‐related biomarkers, molecular classification, and immune infiltration in diabetic ulcers with validation

Metabolism‐related biomarkers, molecular classification, and immune infiltration in diabetic ulcers with validation

Genetic Variants in PHACTR1 & LPL Mediate Restenosis Risk in Coronary Artery Patients

Negative regulator NLRC3: Its potential role and regulatory mechanism in immune response and immune-related diseases

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