PLAGL1 overexpression induces cytoplasmic DNA accumulation that triggers cGAS/STING activation DOI Creative Commons

Cheng Li,

Lingyan Qiao,

Juan Ge

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(19)

Published: Oct. 1, 2024

Abstract Pancreatic β‐cell damage mediated by apoptosis is believed to be a main trigger of type 1 diabetes mellitus (T1DM), which proposed as an organ‐specific autoimmune disease T cells. Nonetheless, the fundamental origins T1DM remain uncertain. Here, we illustrate that increase in PLAGL1 expression induces apoptosis, evidenced mitochondrial membrane impairment and nucleolar degradation. The gene levels from cDNA samples were determined using qRT‐PCR method. Western blot Co‐immunoprecipitation applied for protein interactions, respectively. Flow cytometry TUNEL assay used detect pancreatic β cell apoptosis. Female NOD/LtJ mice with recent‐onset has been vivo studies. Glucose‐stimulated insulin secretion (GSIS) glucose tolerance test (GTT) method islet function assessment. Haematoxylin Eosin (H&E) Immunohistochemistry (IHC) performed evalute histological improvement beta. Subsequent cytoplasmic DNA accumulation triggers senser, cyclic guanosine monophosphate‐AMP synthase (cGAS)‐stimulator interferon genes (STING) pathway. STING activation further stimulates downstream IRF3 NF‐kB pathways, thus boost type‐I signalling inflammation. These findings elucidate molecular mechanism linking induced suggest potential benefit targeting cGAS/STING treatment.

Language: Английский

PLAGL1 overexpression induces cytoplasmic DNA accumulation that triggers cGAS/STING activation DOI Creative Commons

Cheng Li,

Lingyan Qiao,

Juan Ge

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(19)

Published: Oct. 1, 2024

Abstract Pancreatic β‐cell damage mediated by apoptosis is believed to be a main trigger of type 1 diabetes mellitus (T1DM), which proposed as an organ‐specific autoimmune disease T cells. Nonetheless, the fundamental origins T1DM remain uncertain. Here, we illustrate that increase in PLAGL1 expression induces apoptosis, evidenced mitochondrial membrane impairment and nucleolar degradation. The gene levels from cDNA samples were determined using qRT‐PCR method. Western blot Co‐immunoprecipitation applied for protein interactions, respectively. Flow cytometry TUNEL assay used detect pancreatic β cell apoptosis. Female NOD/LtJ mice with recent‐onset has been vivo studies. Glucose‐stimulated insulin secretion (GSIS) glucose tolerance test (GTT) method islet function assessment. Haematoxylin Eosin (H&E) Immunohistochemistry (IHC) performed evalute histological improvement beta. Subsequent cytoplasmic DNA accumulation triggers senser, cyclic guanosine monophosphate‐AMP synthase (cGAS)‐stimulator interferon genes (STING) pathway. STING activation further stimulates downstream IRF3 NF‐kB pathways, thus boost type‐I signalling inflammation. These findings elucidate molecular mechanism linking induced suggest potential benefit targeting cGAS/STING treatment.

Language: Английский

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