Mechanistic Regulation of Wnt Pathway-Related Progression of Chronic Obstructive Pulmonary Disease Airway Lesions

Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic disease associated with inflammation and structural changes in the airways and lungs, resulting from a combination of genetic and environmental factors. This interaction highlights significant genes in early life, particularly those involved in lung development, such as the Wnt signaling pathway. The Wnt signaling pathway plays an important role in cell homeostasis, and its abnormal activation can lead to the occurrence of related diseases such as asthma, COPD, and lung cancer. Due to the fact that the Wnt pathway is mechanically sensitive, abnormal activation of the Wnt pathway by mechanical stress contributes to the progression of chronic diseases. But in the context of COPD, it has received little attention. In this review, we aim to summarize the important current evidence on mechanical stress through the Wnt pathway in airway inflammation and structural changes in COPD and to provide potential targets for COPD treatment strategies.

Causal relationship between chronic obstructive pulmonary disease and BMD at different sites: A bidirectional Mendelian randomization study

“…[ 39 ] On the one hand, pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, IL-11, and IL-17, govern bone resorption by promoting osteoclast activity. [ 40 ] On the other hand, these cytokines directly impede bone formation. The Wnt/β-catenin signaling pathway plays a pivotal role in skeletal development, significantly influencing the differentiation of mesenchymal stem cells into mature osteoblasts.…”

“…TNF-α, acting as a key inducer of DKK-1 (a Wnt antagonist), can suppress osteoblast differentiation. [ 40 , 41 ] According to findings from the Xinxiang Rural Cohort Study conducted in China, a decrease in BMD of 0.1 g/cm 2 was associated with a reduction of 53.0 mL in forced vital capacity (FVC) and 33.5 mL in forced expiratory volume in 1 second (FEV1) after adjusting for possible confounding variables using linear regression analysis, which suggests that a decline in BMD is linked to impaired lung function. [ 42 ]…”

Mechanism of action of miR-15a-5p and miR-152-3p in paraquat-induced pulmonary fibrosis through Wnt/β-catenin signaling mediation

“…The highly conserved Wnt gene, discovered in 1982, encodes a lipid-modified glycoprotein known as the Wnt protein, which consists of 350–400 amino acids ( Ng et al, 2019 ). To date, 19 Wnt proteins have been identified as ligands that bind to the Frizzled (FZD) receptor, low-density lipoprotein receptor-related protein (LRP) receptor, and other receptors on the cell surface to activate signaling pathways with various functions during embryonic and adult development ( Liu, Huo & Cheng, 2023 ) ( Fig. 1 ).…”

WISP1 induces the expression of macrophage migration inhibitory factor in human lung fibroblasts through Src kinases and EGFR-activated signaling pathways

“…Moreover, WISP1 has been found to be increased in alveolar epithelium type II cells in patients with idiopathic pulmonary fibrosis (IPF) and correlates with (myo)fibroblast activation, ECM deposition, and epithelial-mesenchymal transition ( 13 – 15 ). Furthermore, it has been reported that β-catenin signaling contributes to ECM production by lung fibroblasts and their differentiation to myofibroblasts in chronic obstructive pulmonary disease (COPD) ( 24 , 25 ). On the other hand, suppressed Wnt/β-catenin signaling has been suggested to play an essential role in airway inflammation in COPD by promoting the production of inflammatory cytokines via a peroxisome proliferator-activated receptor-δ/p38 signaling pathway in airway epithelial cells ( 26 ).…”