ZC3H4 mediates silica-induced EndoMT via ER stress and autophagy

Jiang, Rong; Han, Lei; Gao, Qianqian; Chao, Jie

doi:10.1016/j.etap.2021.103605

Cited by 9 publications

(6 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CT imaging of the mouse chest and hematoxylin and eosin (H&E) staining showed obvious collagen deposition and PF in mice 56 days after silica instillation (Fig. 1a ), which is consistent with previous reports 18 , 19 . Furthermore, a pulmonary function test was performed, and it was found that several pulmonary function indicators, including inspiratory capacity (IC, which is the volume inspired during slow inspiration), the expiratory reserve volume (ERV), forced vital capacity (FVC, which is the volume expired during fast expiration), and functional residual capacity (FRC), were decreased in the mice (Fig.…”

Section: Resultssupporting

confidence: 91%

Macrophage-derived GPNMB trapped by fibrotic extracellular matrix promotes pulmonary fibrosis

et al. 2023

Self Cite

View full text Add to dashboard Cite

Pulmonary fibrosis (PF) is a form of progressive lung disease characterized by chronic inflammation and excessive extracellular matrix (ECM) deposition. However, the protein changes in fibrotic ECM during PF and their contribution to fibrosis progression are unclear. Here we show that changes in expression of ECM components and ECM remodeling had occurred in silica-instilled mice. The macrophage-derived glycoprotein nonmetastatic melanoma protein B (GPNMB) captured by fibrotic ECM may activate resident normal fibroblasts around the fibrotic foci. Functional experiments demonstrated the activation of fibroblasts in fibrotic ECM, which was alleviated by GPNMB-neutralizing antibodies or macrophage deletion in the ECM of silica-instilled mice. Moreover, the Serpinb2 expression level was increased in fibroblasts in fibrotic ECM, and the expression of CD44 was increased in silica-instilled mice. In conclusion, macrophage-derived GPNMB is trapped by fibrotic ECM during transport and may activate fibroblasts via the CD44/Serpinb2 pathway, thus leading to the further development of fibrosis.

show abstract

Section: Resultssupporting

confidence: 91%

Macrophage-derived GPNMB trapped by fibrotic extracellular matrix promotes pulmonary fibrosis

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…The CT imaging of the mouse chest and hematoxylin and eosin (H&E) staining showed obvious collagen deposition and PF in mice 56 days after silica instillation (Fig. 1A), which is consistent with previous reports (Cheng et al, 2021b;Jiang et al, 2021). Furthermore, a pulmonary function test was performed, and it was found that several pulmonary function indicators, including inspiratory capacity (IC, the volume inspired during slow inspiration), the expiratory reserve volume (ERV), forced vital capacity (FVC, the volume expired during fast expiration) and functional residual capacity (FRC), were signi cantly decreased in the mice (Fig.…”

Section: Fibrotic Ecm Affects Normal Lung Broblast Function In Silico...supporting

confidence: 92%

Macrophage-derived GPNMB Trapped by Fibrotic Extracellular Matrix Promotes Pulmonary Fibrosis

Wang¹,

Zhang²,

Yuan

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Pulmonary fibrosis (PF) is a form of progressive lung disease characterized by chronic inflammation and excessive extracellular matrix (ECM) deposition. The pulmonary ECM undergoes profound changes during fibrosis. However, the protein changes that occur in fibrotic ECM during silica-induced progressive PF and their contribution to fibrosis progression are unclear. Here, we established a model of progressive PF induced by silica, observed the effect of fibrotic ECM on normal fibroblast activation and explored the possible mechanism. Proteomic analysis of the ECM revealed that obvious changes in the expression of ECM components and ECM remodeling occurred. Single-cell RNA sequencing (scRNA-seq) combined with spatial transcriptomics revealed that during transport, macrophage-derived glycoprotein nonmetastatic melanoma protein B (GPNMB) captured by fibrotic ECM may activate resident normal fibroblasts around fibrotic foci. Functional experiments showed activation of normal fibroblasts in fibrotic ECM, which was alleviated by GPNMB-neutralizing antibodies or macrophage deletion in the ECM of silica-instilled mice, implying that macrophage-derived GPNMB may contribute to progressive PF. Transcriptome analysis showed that the Serpinb2 expression level was increased in fibroblasts in fibrotic ECM, and the expression of CD44, a cell receptor for GPNMB, was increased in mice after silica instillation according to scRNA-seq combined with spatial transcriptomics. Therefore, macrophage-derived GPNMB is trapped by fibrotic ECM during transport and may activate fibroblasts via the CD44/Serpinb2 pathway, leading to further development of fibrosis.

show abstract

“…Meanwhile, MCPIP1-siRNA reversed silica-induced autophagy and apoptosis of macrophages [ 31 , 32 ]. Like MCPIP1, zinc finger CCCH-type containing 4 protein (ZC3H4) greatly encouraged the autophagy level, further affecting epithelial-mesenchymal transition (EMT) in endothelial cells [ 33 , 34 , 35 ]. Concretely, ZC3H4 can be activated in multiple ways: (1) the competitive combination of circZC3H4 and miR-212 [ 36 ]; (2) the transcription of ZC3H4 mRNA (which may be caused by phosphorylation of Ets-like protein-1 (Elk-1)) [ 37 ].…”

Section: Autophagy Is An Essential Way Of Programmed Cell Death During Silicotic Progressionmentioning

confidence: 99%

“…Moreover, Bcl-2-binding component 3 (BBC3), a potent activator of apoptosis that also belongs to the Bcl-2 family [ 99 ], may inhibit the binding of BECN1 and Bcl-2 competitively, thereby facilitating silica-induced macrophage autophagy activity [ 100 ]. In addition, a widely accepted stimulating factor to mediate apoptosis, ER stress, may also stimulate autophagy activity in the development of silicosis, caused by the excessive accumulation of unfolded proteins in the endoplasmic reticulum [ 33 , 101 ].…”

Section: The Crosstalk Among Autophagy Apoptosis and Pyroptosis In Silicotic Fibrosis Needs To Be Further Discussedmentioning

confidence: 99%

The Mechanism and Effect of Autophagy, Apoptosis, and Pyroptosis on the Progression of Silicosis

Tan

Chen

2021

IJMS

View full text Add to dashboard Cite

Silicosis remains one of the most severe pulmonary fibrotic diseases worldwide, caused by chronic exposure to silica dust. In this review, we have proposed that programmed cell death (PCD), including autophagy, apoptosis, and pyroptosis, is closely associated with silicosis progression. Furthermore, some autophagy, apoptosis, or pyroptosis-related signaling pathways or regulatory proteins have also been summarized to contribute greatly to the formation and development of silicosis. In addition, silicosis pathogenesis depends on the crosstalk among these three ways of PCD to a certain extent. In summary, more profound research on these mechanisms and effects may be expected to become promising targets for intervention or therapeutic methods of silicosis in the future.

show abstract

ZC3H4 mediates silica-induced EndoMT via ER stress and autophagy

Cited by 9 publications

References 40 publications

Macrophage-derived GPNMB trapped by fibrotic extracellular matrix promotes pulmonary fibrosis

Macrophage-derived GPNMB trapped by fibrotic extracellular matrix promotes pulmonary fibrosis

Macrophage-derived GPNMB Trapped by Fibrotic Extracellular Matrix Promotes Pulmonary Fibrosis

The Mechanism and Effect of Autophagy, Apoptosis, and Pyroptosis on the Progression of Silicosis

Contact Info

Product

Resources

About