Decreased Imiquimod-Induced Psoriasis-Like Skin Inflammation in a Novel MvdF250S/+ Knock-In Mouse Model

La, Yune; Wong, Wenghong; Peng, Kexin; Zhang, Tian; Pan, Jiewen; Sun, Ruilin; Luan, Jing; Yan, Kexiang; Zhang, Qiaoan; Zhang, Zhenghua

doi:10.1007/s10753-023-01828-z

Cited by 3 publications

(1 citation statement)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MVD catalyzes the conversion of mevalonate diphosphate to isopentenyl diphosphate, which is an early step in cholesterol biosynthesis ( 34 ). MVD and the mevalonate pathway are crucial for macrophage survival and play an important role in the synthesis and release of inflammatory mediators, contributing to pro-inflammatory responses of macrophages ( 35 ).…”

Section: The Effect Of Mtb Infection On Macrophage Cholesterol Metabo...mentioning

confidence: 99%

The impact of Mycobacterium tuberculosis on the macrophage cholesterol metabolism pathway

Chen,

Kong,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen capable of adapting and surviving within macrophages, utilizing host nutrients for its growth and replication. Cholesterol is the main carbon source during the infection process of Mtb. Cholesterol metabolism in macrophages is tightly associated with cell functions such as phagocytosis of pathogens, antigen presentation, inflammatory responses, and tissue repair. Research has shown that Mtb infection increases the uptake of low-density lipoprotein (LDL) and cholesterol by macrophages, and enhances de novo cholesterol synthesis in macrophages. Excessive cholesterol is converted into cholesterol esters, while the degradation of cholesterol esters in macrophages is inhibited by Mtb. Furthermore, Mtb infection suppresses the expression of ATP-binding cassette (ABC) transporters in macrophages, impeding cholesterol efflux. These alterations result in the massive accumulation of cholesterol in macrophages, promoting the formation of lipid droplets and foam cells, which ultimately facilitates the persistent survival of Mtb and the progression of tuberculosis (TB), including granuloma formation, tissue cavitation, and systemic dissemination. Mtb infection may also promote the conversion of cholesterol into oxidized cholesterol within macrophages, with the oxidized cholesterol exhibiting anti-Mtb activity. Recent drug development has discovered that reducing cholesterol levels in macrophages can inhibit the invasion of Mtb into macrophages and increase the permeability of anti-tuberculosis drugs. The development of drugs targeting cholesterol metabolic pathways in macrophages, as well as the modification of existing drugs, holds promise for the development of more efficient anti-tuberculosis medications.

show abstract

Section: The Effect Of Mtb Infection On Macrophage Cholesterol Metabo...mentioning

confidence: 99%

The impact of Mycobacterium tuberculosis on the macrophage cholesterol metabolism pathway

Chen,

Kong,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

Establishment of a Mouse Model for Porokeratosis Due to Mevalonate Diphosphate Decarboxylase Deficiency

Peng,

Wong,

Zhang

et al. 2024

Skin Research and Technology

View full text Add to dashboard Cite

IntroductionPorokeratosis (PK) is an autoinflammatory keratinization disease (AIKD) characterized by circular or annular skin lesions with a hyperkeratotic rim, pathologically shown as the cornoid lamella. Four genes that cause PK are associated with the mevalonate (MV) pathway. In Chinese PK patients, mevalonate diphosphate decarboxylase (MVD) is the most common causative gene. The lack of an animal model has greatly limited research on PK pathogenesis.Materials and MethodsIn this research, we constructed K14‐CreERT2‐Mvdfl/fl mice using the Cre‐LoxP system to create a mouse model for in‐depth studies of PK. The Epidermal Mvd gene was knocked out by intraperitoneal injection of Tamoxifen (TAM). Pathology, immunohistochemistry, RNA‐seq, and Western Blot analysis were performed.ResultsSkin lesions appeared following Mvd deficiency, and pathological examination revealed the characteristic cornoid lamella, as well as cutaneous inflammation. Furthermore, we observed elevated levels of IL‐17A and IL‐1β, and a decreased Loricrin level in epidermal Mvd‐deficient mice. Compared with the wild‐type (WT) group, Mvd deficiency activated the expression of lipid metabolism‐related proteins.ConclusionWe developed the first mouse model for PK research, enabling further studies on disease development and treatment approaches.

show abstract

Application and perspective of CRISPR/Cas9 genome editing technology in human diseases modeling and gene therapy

Zhang,

Li,

Jin

2024

Front. Genet.

View full text Add to dashboard Cite

The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) mediated Cas9 nuclease system has been extensively used for genome editing and gene modification in eukaryotic cells. CRISPR/Cas9 technology holds great potential for various applications, including the correction of genetic defects or mutations within the human genome. The application of CRISPR/Cas9 genome editing system in human disease research is anticipated to solve a multitude of intricate molecular biology challenges encountered in life science research. Here, we review the fundamental principles underlying CRISPR/Cas9 technology and its recent application in neurodegenerative diseases, cardiovascular diseases, autoimmune related diseases, and cancer, focusing on the disease modeling and gene therapy potential of CRISPR/Cas9 in these diseases. Finally, we provide an overview of the limitations and future prospects associated with employing CRISPR/Cas9 technology for diseases study and treatment.

show abstract

Decreased Imiquimod-Induced Psoriasis-Like Skin Inflammation in a Novel MvdF250S/+ Knock-In Mouse Model

Cited by 3 publications

References 35 publications

The impact of Mycobacterium tuberculosis on the macrophage cholesterol metabolism pathway

The impact of Mycobacterium tuberculosis on the macrophage cholesterol metabolism pathway

Establishment of a Mouse Model for Porokeratosis Due to Mevalonate Diphosphate Decarboxylase Deficiency

Application and perspective of CRISPR/Cas9 genome editing technology in human diseases modeling and gene therapy

Contact Info

Product

Resources

About