2019年7月15日 · Cytokine-induced MUC5B expression in HAE cells was inhibited by KIRA6 and XBP1 CRISPR-Cas9. Conclusions: A positive feedback bistable ERN2-XBP1S pathway regulates MUC5B-dominated mucus obstruction in IPF, providing an unfolded protein response-dependent mechanism linking the MUC5B promoter rs35705950 polymorphism with IPF pathogenesis.

This study provides mechanistic insights into the pathophysiology of IPF and therapeutic approaches to reduce mucin expression following high-strength, irreversible activation of the unfolded protein response in IPF.

2016年4月7日 · IRE1α has been known to splice X-box binding protein 1 (XBP1) mRNA, which is induced by ATF6 under ER stress. This spliced XBP1 mRNA is translated into the active transcription factor that...

2025年1月2日 · Polymeric mucin production has been best studied in the context of the IRE-1 pathway. Unfolded proteins stimulate IRE-1 ribonuclease activity to remove a normally unspliced intron in XBP1, enabling translation of a transcription factor that upregulates corrective and cytotoxic ER stress responses (78, 79).

2018年3月1日 · Using fluorescent immunohistochemistry, we profiled autophagy (LC3βII) and UPR (BIP and XBP1) markers in human non-IPF and IPF lung tissue. TGF-β 1 -induced collagen 1α2 and fibronectin protein production was significantly higher in IPF lung fibroblasts compared with lung and airway fibroblasts from non-IPF donors.

EGFP and XBP1 oligonucleotides for the sgRNA guide sequence (synthesized by Eurofins Genomics) were phosphorylated using T4 polynucleotide kinase (cat#EK0031, ThermoFisher) at 37 °C for 30 minutes and then annealed by heating to 95 °C for 5 minutes and

Cytokine-induced MUC5B expression in HAE cells was inhibited by KIRA6 and XBP1 CRISPR-Cas9. Conclusions: A positive feedback bistable ERN2–XBP1S pathway regulates MUC5B-dominated mucus obstruction in IPF, providing an unfolded protein response–dependent mechanism linking the MUC5B promoter rs35705950 polymorphism with IPF pathogenesis.

2019年4月11日 · High levels of ERN2 and XBP1S were associated with excessive MUC5B mRNAs in distal airways of human IPF lungs. Cytokine-induced MUC5B expression in HAE cells was inhibited by KIRA6 and XBP1...

Indeed, it has been shown that markers of ER stress, such as BiP and XBP1, are elevated in the lung tissue of IPF patients [52,54]. In particular, BiP, an ER chaperon that participates in the docking of UPR sensors, and spliced XPB1, a transcription factor responsible for ER-associated degradation, are considered reliable activation markers of ...

2019年7月7日 · Conclusions: A positive feedback bistable ERN2–XBP1S pathway regulates MUC5B-dominated mucus obstruction in IPF, providing an unfolded protein response–dependent mechanism linking the MUC5B promoter rs35705950 polymorphism with IPF pathogenesis. Inhibiting ERN2-dependent pathways/elements may provide a therapeutic option for IPF.