Mitochondria-Regulated Information Processing Nanosystem Promoting Immune Cell Communication for Liver Fibrosis Regression.
Tingting CheXiaopeng YangYuanyuan ZhangYin ZhengYufei ZhangXinge ZhangZhongming WuPublished in: Small (Weinheim an der Bergstrasse, Germany) (2024)
Liver fibrosis is a coordinated response to tissue injury that is mediated by immune cell interactions. A mitochondria-regulated information-processing (MIP) nanosystem that promotes immune cell communication and interactions to inhibit liver fibrosis is designed. The MIP nanosystem mimics the alkaline amino acid domain of mitochondrial precursor proteins, providing precise targeting of the mitochondria. The MIP nanosystem is driven by light to modulate the mitochondria of hepatic stellate cells, resulting in the release of mitochondrial DNA into the fibrotic microenvironment, as detected by macrophages. By activating the STING signaling pathway, the developed nanosystem-induced macrophage phenotype switches to a reparative subtype (Ly6C low ) and downstream immunostimulatory transcriptional activity, fully restoring the fibrotic liver to its normal tissue state. The MIP nanosystem serves as an advanced information transfer system, allowing precise regulation of trained immunity, and offers a promising approach for effective liver fibrosis immunotherapy with the potential for clinical translation.
Keyphrases
- liver fibrosis
- mitochondrial dna
- signaling pathway
- cell death
- reactive oxygen species
- induced apoptosis
- endoplasmic reticulum
- transcription factor
- copy number
- amino acid
- health information
- cell cycle arrest
- oxidative stress
- adipose tissue
- gene expression
- idiopathic pulmonary fibrosis
- stem cells
- epithelial mesenchymal transition
- healthcare
- pi k akt
- cell proliferation
- high glucose
- drug delivery
- risk assessment
- heat stress
- heat shock
- social media