Cellular and Molecular Mechanisms in Idiopathic Pulmonary Fibrosis

Advances in respiratory medicine, Journal Year: 2023, Volume and Issue: 91(1), P. 26 - 48

Published: Jan. 31, 2023

The respiratory system is a well-organized multicellular organ, and disruption of cellular homeostasis or abnormal tissue repair caused by genetic deficiency exposure to risk factors lead life-threatening pulmonary disease including idiopathic fibrosis (IPF). Although there no clear etiology as the name reflected, its pathological progress closely related uncoordinated molecular signals. Here, we review advances in our understanding role lung cells IPF pathology epithelial cells, mesenchymal stem fibroblasts, immune endothelial cells. These summarize various cell components signaling pathways pathogenesis fibrosis, which helpful further study mechanism disease, provide new opportunities for prevention treatment, expected improve survival rate quality life patients.

Language: Английский

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The Genetic Landscape of Familial Pulmonary Fibrosis

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2023, Volume and Issue: 207(10), P. 1345 - 1357

Published: Jan. 9, 2023

Rationale and Objectives: Up to 20% of idiopathic interstitial lung disease is familial, referred as familial pulmonary fibrosis (FPF). An integrated analysis FPF genetic risk was performed by comprehensively evaluating for rare variants (RVs) in a large cohort kindreds. Methods: Whole-exome sequencing and/or candidate gene from affected individuals 569 kindreds performed, followed cosegregation kindreds, burden analysis, gene-based scoring, cell-type enrichment coexpression network construction. Measurements Main Results: It found that 14.9–23.4% could be explained RVs genes previously linked FPF, predominantly telomere-related genes. New were identified small number families—including SYDE1, SERPINB8, GPR87, NETO1—and tools developed evaluation prioritization RV-containing across Several pathways enriched including focal adhesion mitochondrial complex I assembly. By combining single-cell transcriptomics with prioritized genes, expression discovered smooth muscle cells, type II alveolar epithelial endothelial cells. Conclusions: In the most comprehensive study date, prevalence known FPF-related defined, new relevant identified. However, shared multiple not identified, thereby suggesting heterogeneous involving variety mediate

Language: Английский

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Naringin regulates endoplasmic reticulum stress and mitophagy through the ATF3/PINK1 signaling axis to alleviate pulmonary fibrosis

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2023, Volume and Issue: 396(6), P. 1155 - 1169

Published: Jan. 23, 2023

Language: Английский

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Exosomal STIMATE derived from type II alveolar epithelial cells controls metabolic reprogramming of tissue-resident alveolar macrophages

Theranostics, Journal Year: 2023, Volume and Issue: 13(3), P. 991 - 1009

Published: Jan. 1, 2023

Background: Complete abolition of alveolar epithelial cells (AECs) is characteristic end-stage lung disease.Transplantation therapy type II AECs (AEC-IIs) or AEC-IIs-derived exosomes (ADEs) have been proposed as a means repairing injury and preventing fibrosis.However, the mechanism by which ADEs balances airway immunity alleviates damage fibrosis remains unknown.Methods: We investigated STIM-activating enhancer-positive (STIMATE + ADEs) in 112 ALI/ARDS 44 IPF patients, observed correlation between STIMATE subpopulation proportion metabolic status tissue-resident macrophages (TRAMs).We constructed conditional knockout mice sftpc , was specifically knocked out mouse AEC-IIs effects deficiency on disease progression, immune selection switching TRAMs.We BLM-induced model to observe salvage treatment damage/fibrosis progression with supplementation.Results: In clinical analysis, distinct phenotypes AMs ALI/ARFS were significantly perturbed ADEs.The TRAMs lungs imbalanced, resulting spontaneous inflammatory respiratory disorders.STIMATE are taken up regulate high Ca 2+ responsiveness long-term signal transduction, maintains M2-like immunophenotype metabolism selection.This involves calcineurin (CaN)-PGC-1α pathway mediated mitochondrial biogenesis mtDNA coding.In bleomycin-induced model, supplementation inhaled lessened early acute injury, prevented advanced fibrosis, alleviated ventilatory impairment reduced mortality.

Language: Английский

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Ageing of skeletal muscle extracellular matrix and mitochondria: finding a potential link

Annals of Medicine, Journal Year: 2023, Volume and Issue: 55(2)

Published: Aug. 29, 2023

Aim: To discuss the progress of extracellular matrix (ECM) characteristics, mitochondrial homeostasis, and their potential crosstalk in pathogenesis sarcopenia, a geriatric syndrome characterized by generalized progressive reduction muscle mass, strength, physical performance.Methods: This review focuses on anatomy physiology skeletal muscle, alterations ECM mitochondria during ageing, role interplay between sarcopenia.Results: Emerging evidence points to clear various tissues organs. Under ageing process, undergoes changes composition properties that may mediate via systematic metabolism, ROS, SPARC pathway, AMPK/PGC-1α signalling, which turn exacerbate degeneration. However, precise effects such pathobiology particularly have not yet been fully understood.Conclusion: The are partially responsible for worsened function process. A deeper understanding interactions sarcopenic patients can help prevent sarcopenia improve its prognoses.

Language: Английский

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