Publications by authors named "P L Splinter"
Article Synopsis
- - Senescent cells release inflammatory signals known as the senescence-associated secretory phenotype (SASP), which are linked to aging and tissue dysfunction.
- - Mitochondrial RNA (mtRNA) accumulates in these cells and activates RNA sensors, triggering the aggregation of MAVS and enhancing SASP production.
- - Targeting the RNA sensors and understanding the role of proteins like BAX and BAK can potentially reduce SASP factors and age-related inflammation, suggesting new treatment approaches for conditions like Metabolic Dysfunction Associated Steatohepatitis (MASH).
Background & Aims: We reported that cholangiocyte senescence, regulated by the transcription factor ETS proto-oncogene 1 (ETS1), is a pathogenic feature of primary sclerosing cholangitis (PSC). Furthermore, histone 3 lysine 27 is acetylated at senescence-associated loci. The epigenetic readers, bromodomain and extra-terminal domain (BET) proteins, bind acetylated histones, recruit transcription factors, and drive gene expression.
View Article and Find Full Text PDFBackground & Aims: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by peribiliary inflammation and fibrosis. Cholangiocyte senescence is a prominent feature of PSC. Here, we hypothesize that extracellular vesicles (EVs) from senescent cholangiocytes influence the phenotype of target cells.
View Article and Find Full Text PDFPrimary sclerosing cholangitis (PSC) is an idiopathic, progressive cholangiopathy. Cholangiocyte senescence is important in PSC pathogenesis, and we have previously reported that senescence is regulated by the transcription factor ETS proto-oncogene 1 (ETS1) and associated with overexpression of BCL2 like 1 (BCL2L1 or BCL-xL), an anti-apoptotic BCL2-family member. Here, we further explored the mechanisms regulating BCL-xL-mediated, apoptosis resistance in senescent cholangiocytes and uncovered that ETS1 and the histone acetyltransferase E1A-binding protein P300 (EP300 or p300) both promote transcription.
View Article and Find Full Text PDFArticle Synopsis
- Macrophages play a significant role in cholestatic liver disease, particularly in conditions like primary sclerosing cholangitis (PSC), as their presence correlates with liver injury and fibrosis.
- In experimental models, researchers found an increase in pro-inflammatory (M1) and alternatively-activated (M2) macrophages around bile ducts in PSC-affected livers, indicating their active involvement in disease progression.
- Targeting the recruitment of macrophages through genetic deletion or pharmacological agents showed promise in reducing liver injury and fibrosis, suggesting that modulating macrophage activity could be a potential therapeutic strategy for PSC and similar liver diseases.