The study of GSDMB in pathogenesis of psoriasis vulgaris

Ji, Xiaojuan; Chen, Huaqing; Xie, Lihua; Chen, Shiqi; Huang, Shan; Yang, Huifang; Yang, Tao; Ye, Xiaoying; Zeng, Zhao-Lin; Wan, Chunlei; Li, Longnian

doi:10.1371/journal.pone.0279908

Cited by 5 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gsdmb and Gsdmc , expressed in human keratinocytes, were also suggested to contribute to keratinocyte differentiation and cornification (Lachner et al 2017 ). In addition to skin build-up and maintenance, gasdermins, notably Gsdmb and Gsdmd , were shown to affect T-cell differentiation and function, as well as macrophage infiltration, protecting the skin against bacterial infections and contributing to the pathophysiology of skin diseases, such as psoriasis or skin fibrosis (Liu et al 2021 ; Yang et al 2022 ; Ji et al 2023 ). Our study of the gasdermin family ( Gsdma , Gsdmb , Gsdmc , and Gsdmd ) revealed some very different scenarios regarding the conservation status of these genes.…”

Section: Resultsmentioning

confidence: 99%

Decay of Skin-Specific Gene Modules in Pangolins

et al. 2023

View full text Add to dashboard Cite

The mammalian skin exhibits a rich spectrum of evolutionary adaptations. The pilosebaceous unit, composed of the hair shaft, follicle, and the sebaceous gland, is the most striking synapomorphy. The evolutionary diversification of mammals across different ecological niches was paralleled by the appearance of an ample variety of skin modifications. Pangolins, order Pholidota, exhibit keratin-derived scales, one of the most iconic skin appendages. This formidable armor is intended to serve as a deterrent against predators. Surprisingly, while pangolins have hair on their abdomens, the occurrence of sebaceous and sweat glands is contentious. Here, we explore various molecular modules of skin physiology in four pangolin genomes, including that of sebum production. We show that genes driving wax monoester formation, Awat1/2, show patterns of inactivation in the stem pangolin branch, while the triacylglycerol synthesis gene Dgat2l6 seems independently eroded in the African and Asian clades. In contrast, Elovl3 implicated in the formation of specific neutral lipids required for skin barrier function is intact and expressed in the pangolin skin. An extended comparative analysis shows that genes involved in skin pathogen defense and structural integrity of keratinocyte layers also show inactivating mutations: associated with both ancestral and independent pseudogenization events. Finally, we deduce that the suggested absence of sweat glands is not paralleled by the inactivation of the ATP-binding cassette transporter Abcc11, as previously described in Cetacea. Our findings reveal the sophisticated and complex history of gene retention and loss as key mechanisms in the evolution of the highly modified mammalian skin phenotypes.

show abstract

Section: Resultsmentioning

confidence: 99%

Decay of Skin-Specific Gene Modules in Pangolins

et al. 2023

View full text Add to dashboard Cite

show abstract

“…In the second study, the expression of GSDMB in psoriatic epidermis was decreased compared to healthy skin ( Ji et al, 2023 ). The authors of the latter study stated that decreased GSDMB in psoriasis leads to inhibition of cell proliferation and stimulates apoptosis ( Ji et al, 2023 ). Taking into account that the lack of GSDMB had been linked to decreased cell proliferation in the past ( Rana et al, 2022 ), psoriasis is known for decreased apoptosis ( Shou et al, 2021 ), and those authors observed downregulation of GSDMB, these results do not correspond to psoriasis pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Gasdermin B (GSDMB) in psoriatic patients–a preliminary comprehensive study on human serum, urine and skin

Nowowiejska,

Baran,

Pryczynicz

et al. 2024

Front. Mol. Biosci.

View full text Add to dashboard Cite

Psoriasis is one of the most common skin diseases and a crucial issue to manage in contemporary dermatology. The search for the details of its pathogenesis, markers and treatment is continuously ongoing. Our aim was to investigate the role of gasdermin B (GSDMB) in psoriasis, the second protein from the gasdermin family, involved in cell death and proliferation. GSDMB serum and urinary concentrations have never been studied in psoriatics, neither tissue expression of GSDMB by immunohistochemistry. The study included 60 psoriatic patients and 30 volunteers without dermatoses as controls. The serum and urinary GSDMB were evaluated by ELISA. Tissue expression of GSDMB was analyzed by immunohistochemistry. The serum and absolute urine concentrations of GSDMB were significantly higher in psoriatic patients than controls without skin diseases (p = 0.0137, p = 0.039 respectively). Urinary GSDMB/creatinine concentration ratio was significantly lower in patients compared to controls (p = 0.0241). The expression of GSDMB in the dermis and epidermis was significantly more prevalent in psoriatic plaque compared to the non-lesional skin and healthy skin of controls (p = 0.0012, p = 0.017, respectively). Serum GSDMB correlated positively with the age of patients (R = 0.41; p = 0.001). Our study adds to the current state of knowledge about psoriasis concerning the potential involvement of GSDMB. Possibly it could be engaged in keratinocytes migration, which requires further research. Elevated serum GSDMB and decreased urinary GSDMB/creatinine concentration ratio could potentially be investigated as psoriasis biomarkers. GSDMB could be investigated in the future as a potential therapeutic target.

show abstract

“… [ 63 ] IFI27 Keratinocytes This study demonstrates that IFI27 is required for cell proliferation in vitro and in vivo, and that if27 may be a suitable target for the development of a novel anti-psoriasis therapy [ 70 ] SERPINB2 Neutrophils Since SERPINB2 expression is positively correlated with psoriasis severity, it may be used as a biomarker for psoriasis [ 71 ] Notch-1 Endothelial cells The Notch-ligand receptor pathway may regulate vascular dysfunction and pro-inflammatory mechanisms involved in the pathogenesis of psoriasis, suggesting that targeted blockade of this pathway may have important therapeutic implications. [ 72 ] Gasdermin B Keratinocytes This study suggests that Gasdermin B may be associated with psoriasis [ 73 ] βTrCP NF-κB Keratinocytes βTrCP is involved in the NF-κB signaling mediated-, psoriasis-related inflam-mation and represent a novel target for developing agents to treat psoriasis. [ 74 ] bFGF JNK/SAPK Endothelial cells Modulation of the JNK/SAPK signaling pathway may be a promising therapeutic approach for treating angiogenesis-related diseases [ 75 ] STC1 Keratinocytes Targeting STC1 and/or signaling molecules induced by STC1 could be a new therapeutic strategy for controlling diseases involving dysregulation of epidermal and dermal interactions.…”

Section: Discussionmentioning

confidence: 99%

Targeted siRNA Therapy for Psoriasis: Translating Preclinical Potential into Clinical Treatments

Zhao,

Wei

et al. 2024

ITT

View full text Add to dashboard Cite

Psoriasis is a chronic inflammatory skin disease characterized by the excessive proliferation of keratinocytes and heightened immune activation. Targeting pathogenic genes through small interfering RNA (siRNA) therapy represents a promising strategy for the treatment of psoriasis. This mini-review provides a comprehensive summary of siRNA research targeting the pathogenesis of psoriasis, covering aspects such as keratinocyte function, inflammatory cell roles, preclinical animal studies, and siRNA delivery mechanisms. It details recent advancements in RNA interference that modulate key factors including keratinocyte proliferation (Fibroblast Growth Factor Receptor 2, FGFR2 ), apoptosis (Interferon Alpha Inducible Protein 6, G1P3 ), differentiation (Grainyhead Like Transcription Factor 2, GRHL2 ), and angiogenesis (Vascular Endothelial Growth Factor, VEGF ); immune cell infiltration and inflammation (Tumor Necrosis Factor-Alpha, TNF-α ; Interleukin-17, IL-17 ); and signaling pathways ( JAK-STAT , Nuclear Factor Kappa B, NF-κB ) that govern immunopathology. Despite significant advances in siRNA-targeted treatments for psoriasis, several challenges persist. Continued scientific developments promise the creation of more effective and safer siRNA medications, potentially enhancing the quality of life for psoriasis patients and revolutionizing treatments for other diseases. This article focuses on the most recent research advancements in targeting the pathogenesis of psoriasis with siRNA and explores its future therapeutic prospects.

show abstract

The study of GSDMB in pathogenesis of psoriasis vulgaris

Cited by 5 publications

References 27 publications

Decay of Skin-Specific Gene Modules in Pangolins

Decay of Skin-Specific Gene Modules in Pangolins

Gasdermin B (GSDMB) in psoriatic patients–a preliminary comprehensive study on human serum, urine and skin

Targeted siRNA Therapy for Psoriasis: Translating Preclinical Potential into Clinical Treatments

Contact Info

Product

Resources

About