Protein Expression Profile in Rat Silicosis Model Reveals Upregulation of PTPN2 and Its Inhibitory Effect on Epithelial-Mesenchymal Transition by Dephosphorylation of STAT3

Abstract

Silicosis is a chronic occupational lung disease caused by long-term inhalation of crystalline silica particulates. We created a rat model that closely approximates the exposure and development of silicosis in humans. Isobaric tags for relative and absolute quantitation (iTRAQ) technologies we used to identify proteins differentially expressed in activated rat lung tissue. We constructed three lentiviral knockdown vectors and an overexpression vector for the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene to achieve stable long-term expression. A total of 471 proteins were differentially expressed in the silicosis group compared with controls. Twenty upregulated, and eight downregulated proteins exhibited a ≥1.5-fold change relative to controls. We next found that the PTPN2, Factor B, and VRK1 concentrations in silicotic rats silicosis and SiO2-stimulated MLE-12 cells were significantly higher than control groups. More importantly, we found that overexpression of PTPN2 simultaneously decreased the expression of phospho–signal transducer and activator of transcription 3 (p-STAT3) and Vimentin, while increasing E-cadherin expression. The opposite pattern was observed for PTPN2-gene silencing. We identified three proteins with substantially enhanced expression in silicosis. Our study also showed that PTPN2 can inhibit epithelial-mesenchymal transition by dephosphorylating STAT3 in silicosis fibrosis.

Distinct metabolic features in the plasma of patients with silicosis and dust-exposed workers in China: a case–control study

“…The repeated process of phagocytosis, necrosis and rephagocytosis of the cells induces inflammation and activation of the reactive oxygen species system, which is associated with pulmonary interstitial fibrosis [6][7][8]. Proteomic analysis has suggested that some proteins have been found to be closely related to the occurrence and development of silicosis [9,10]. Most proteins were enriched in immune system processes, oxygen transporter activity, phagosome, lysosome and extracellular matrix (ECM)-receptor interactions [11].…”

Global Profiling of Proteome, Lysine Acetylome And Succinylome Identifying Silica Injuries In Mice Lung

“…In this case, we applied TMT proteome to compare the lungs from silicosis mice with healthy controls, and successfully identi ed 1,742 differentially expressed proteins (≥ 1.2-fold change, p < 0.05) in silicosis mice. This is far above previous reports (471 differentially expressed proteins identi ed by iTRAQ [10]), and with highly improved detection precision.…”

“…After that, Na's group [9] reported 196 differentially expressed proteins (fold change ≥ 1.2) in silica-treated broblasts. And in 2020, Juxiang Yuan and his colleagues [10] examined lung tissues of silicosis mice and normal mice and identi ed 471 proteins differentially expressed proteins between the two groups.…”

Glycolytic Reprogramming in Silica-Induced Lung Macrophages and Silicosis Reversed by Ac-SDKP Treatment

“…In previous studies, the mRNA and protein expression levels of LDHA were increased in rats that inhaled silica [ 10 , 11 ]. As the key enzyme in glycolysis, LDHA preferentially converts pyruvate to lactate.…”

“…Our previous studies showed that the mRNA and protein levels of lactate dehydrogenase A (LDHA) were upregulated in rats that inhaled silica [ 10 , 11 ], suggesting a potential role of LDHA in the glycolysis of silicosis. Increased levels of LDHA and its metabolic product, lactate, were found in patients with idiopathic pulmonary fibrosis (IPF).…”