Essential roles of the unfolded protein response in intestinal physiology DOI Creative Commons
Claudio Hetz, Juan Francisco Silva-Agüero, Lisa Ellerby

et al.

eGastroenterology, Journal Year: 2024, Volume and Issue: 2(4), P. e100129 - e100129

Published: Dec. 1, 2024

The intestinal epithelium serves as an essential interface between the host and microbiota, regulating innate adaptive immunity, absorption of nutrients systemic metabolism, mediating bidirectional communication with nervous system. suffers constant challenges to proteostasis machinery due its exposure dynamically changing microbial laden lumenal gut environment high secretory demand placed on multiple epithelial cell types accommodate physiology-especially goblet, enteroendocrine Paneth cells. In all cases, cells require active unfolded protein response (UPR) sustain their physiological function, main pathway that monitors adjusts function changes in environment. A specialised endoplasmic reticulum (ER) stress sensor uniquely expressed lining mucosal surfaces, termed inositol-requiring transmembrane kinase/endoribonuclease β, has specific roles homeostasis, mucus production microbiota. Chronic ER or genetic mutations affecting key UPR mediators contribute occurrence inflammatory bowel disease ulcerative colitis, addition colon cancer. Here, we review recent advances linking physiology disease. Therapeutic strategies alleviate enforce improve ageing diseases are also discussed.

Language: Английский

Glycosylation Regulation by TMEM230 in Aging and Autoimmunity DOI Open Access
Eleonora Piscitelli, Edoardo Abeni,

Cristiana Balbino

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2412 - 2412

Published: March 7, 2025

Aging is often a choice between developing cancer or autoimmune disorders, due in part to loss of self-tolerance immunological recognition rogue-acting tumor cells. Self-tolerance and cell by the immune system are processes very much dependent on specific signatures glycans glycosylated factors present plasma membrane stromal components tissue. Glycosylated generated nearly innumerable variations nature, allowing for immensely diverse role these aging flexibility necessary cellular interactions tissue functionality. In previous studies, we showed that differential expression TMEM230, an endoplasmic reticulum (ER) protein was associated with enzymes regulating glycan synthesis processing glycosylation rheumatoid arthritis synovial using single-cell transcript sequencing. this current study, characterize genes pathways co-modulated all types processing, as well glycosylation. Genes biological molecular hallmarks were mitochondria-dependent oxidative phosphorylation reactive oxygen species synthesis, ER-dependent stress unfolded response, DNA repair (UV response P53 signaling pathways), senescence, glycolysis apoptosis regulation through PI3K-AKT-mTOR have been shown play important roles neurodegeneration (such Parkinson’s Alzheimer’s disease). We propose downregulation TMEM230 RNASET2 may represent paradigm study age-dependent disorders their glycosylation, signaling.

Language: Английский

Citations

0
Essential roles of the unfolded protein response in intestinal physiology DOI Creative Commons
Claudio Hetz, Juan Francisco Silva-Agüero, Lisa Ellerby

et al.

eGastroenterology, Journal Year: 2024, Volume and Issue: 2(4), P. e100129 - e100129

Published: Dec. 1, 2024

The intestinal epithelium serves as an essential interface between the host and microbiota, regulating innate adaptive immunity, absorption of nutrients systemic metabolism, mediating bidirectional communication with nervous system. suffers constant challenges to proteostasis machinery due its exposure dynamically changing microbial laden lumenal gut environment high secretory demand placed on multiple epithelial cell types accommodate physiology-especially goblet, enteroendocrine Paneth cells. In all cases, cells require active unfolded protein response (UPR) sustain their physiological function, main pathway that monitors adjusts function changes in environment. A specialised endoplasmic reticulum (ER) stress sensor uniquely expressed lining mucosal surfaces, termed inositol-requiring transmembrane kinase/endoribonuclease β, has specific roles homeostasis, mucus production microbiota. Chronic ER or genetic mutations affecting key UPR mediators contribute occurrence inflammatory bowel disease ulcerative colitis, addition colon cancer. Here, we review recent advances linking physiology disease. Therapeutic strategies alleviate enforce improve ageing diseases are also discussed.

Language: Английский

Citations

0