Mesenchymal stem cells ameliorate silica‐induced pulmonary fibrosis by inhibition of inflammation and epithelial‐mesenchymal transition

Abstract

Silicosis is a devastating occupational disease caused by long‐term inhalation of silica particles, inducing irreversible lung damage and affecting lung function, without effective treatment. Mesenchymal stem cells (MSCs) are a heterogeneous subset of adult stem cells that exhibit excellent self‐renewal capacity, multi‐lineage differentiation potential and immunomodulatory properties. The aim of this study was to explore the effect of bone marrow‐derived mesenchymal stem cells (BMSCs) in a silica‐induced rat model of pulmonary fibrosis. The rats were treated with BMSCs on days 14, 28 and 42 after perfusion with silica. Histological examination and hydroxyproline assays showed that BMSCs alleviated silica‐induced pulmonary fibrosis in rats. Results from ELISA and qRT‐PCR indicated that BMSCs inhibited the expression of inflammatory cytokines TNF‐α, IL‐1β and IL‐6 in lung tissues and bronchoalveolar lavage fluid of rats exposed to silica particles. We also performed qRT‐PCR, Western blot and immunohistochemistry to examine epithelial‐mesenchymal transition (EMT)–related indicators and demonstrated that BMSCs up‐regulate E‐cadherin and down‐regulate vimentin and extracellular matrix (ECM) components such as fibronectin and collagen Ⅰ. Additionally, BMSCs inhibited the silica‐induced increase in TGF‐β1, p‐Smad2 and p‐Smad3 and decrease in Smad7. These results suggested that BMSCs can inhibit inflammation and reverse EMT through the inhibition of the TGF‐β/Smad signalling pathway to exhibit an anti‐fibrotic effect in the rat silicosis model. Our study provides a new and meaningful perspective for silicosis treatment strategies.

Inositol Alleviates Pulmonary Fibrosis by Promoting Autophagy via Inhibiting the HIF-1α-SLUG Axis in Acute Respiratory Distress Syndrome

“…Lung cell EMT plays an important role in ventilationassociated lung fibrosis, which contributes to the poor outcomes of patients with ARDS. Numerous studies have indicated that inhibition of the EMT process can ameliorate pulmonary fibrosis [24]. Those studies have also shown that inositol suppresses cell motility and invasiveness by inducing cytoskeletal modifications that induce an EMT reversion in breast cancer cells [25], suggesting that inositol can inhibit the EMT process.…”

Potential therapeutic application of mesenchymal stem cells in COVID-19 complications

“…Under normal conditions, these enzymes regulate the levels of angiotensin, converting it into inactive metabolites. Combining viruses with receptors blocks the enzymatic activity of the latter, which results in an increase in the concentration of the hormone inside the cells and ultimately their death [20].…”

“…Absorption of damaged cells results in the release of small alarmins, also known as damage-associated molecular patterns (DAMPs). These molecules are recognized by toll-like receptors located on the surface of dendritic cells and leukocytes [20]. Binding of DAMPs activates in these cells the MyD88 adapter protein-dependent signalling pathway through which the nuclear factor kappa-light-chain-ehancer of activated B cells (NFκB) is activated.…”

miRNA‐34c‐5p targets Fra‐1 to inhibit pulmonary fibrosis induced by silica through p53 and PTEN/PI3K/Akt signaling pathway

“…4 However, the clinical symptoms of the disease develop rapidly, mainly inflammation and systemic features, pathologically dominated by excessive epithelial-mesenchymal transformation (EMT) and extracellular matrix (ECM) effects. 5 This can lead to increased mortality among younger workers. Furthermore, the prognosis of acute silicosis is poor, with patients often progressing to chronic respiratory failure, cor pulmonale, and death.…”

“…Silicosis is caused by long‐term inhalation of significant quantities of free silica dust, an occupational disease primarily characterized by pulmonary fibrosis, which is considered primarily to be a disease with a long incubation period (>20 years) 4 . However, the clinical symptoms of the disease develop rapidly, mainly inflammation and systemic features, pathologically dominated by excessive epithelial‐mesenchymal transformation (EMT) and extracellular matrix (ECM) effects 5 . This can lead to increased mortality among younger workers.…”