Silica Perturbs Primary Cilia and Causes Myofibroblast Differentiation during Silicosis by Reduction of the KIF3A-Repressor GLI3 Complex

Li, Shifeng; Wei, Zhongqiu; Li, Gengxu; Zhang, Qiaodan; Niu, Siyu; Xu, Danfeng; Mao, Na; Chen, Si; Gao, Xuemin; Cai, Wenchen; Zhu, Ying; Zhang, Guizhen; Li, Dan; Xue, Yu; Fang, Yang; Xu, Hong

doi:10.7150/thno.37049

Cited by 14 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This model system readily induced fibrotic remodeling in the lung typical of pulmonary silicosis, as has been reported previously. 18 This included the accumulation of large numbers of silicotic lung nodules, extensive deposition of interstitial collagen, and increased numbers of a-SMA-positive cells (Figure 1A). We also found that Col I and a-SMA protein levels were significantly increased in the lungs of these animals relative to those in controls (p < 0.05; Figure 1B).…”

Section: Silicosis Alters Mirna Expression In the Rat Lungmentioning

confidence: 99%

“…Immunostaining was performed according to published methods. 14,18 In brief, dewaxed tissue sections were treated with 0.3% H 2 O 2 to quench endogenous peroxidases and then subjected to antigen retrieval using a high-pressure method. Samples were incubated overnight at 4 C with a primary antibody against a-SMA (ab32575, Abcam), followed by incubation with a secondary antibody (PV-6000, Beijing Zhongshan Jinqiao Biotechnology, Beijing, China) at 37 C for 30 min before the application of 3,3 0 -diaminobenzidine tetrahydrochloride substrate (ZLI-9018, ZSGB-BIO, Beijing, China).…”

Section: Histology and Immunostainingmentioning

confidence: 99%

“…Brown staining, signifying a-SMApositive cells, was visualized by light microscopy. Co-staining of a-SMA and MATF-A was performed according to our previously published method 18 using primary antibodies against a-SMA (ab7817, Abcam) and MATF-A (A12598, ABclonal).…”

Section: Histology and Immunostainingmentioning

confidence: 99%

“…Western blotting was performed according to standard protocols using a Bicinchonininc acid (BCA) protein concentration determination kit (70-PQ0012, MultiSciences) and primary antibodies against Col I (ab34710, Abcam), a-SMA (ab32575, Abcam), SRF (AF6160, Affinity), MATF-A (A12598, ABclonal), and a-tubulin (sc-53029, Santa Cruz Biotechnology). 13,18 Membranes were probed with a peroxidase-conjugated, affinity-purified secondary antibody to rabbit/mouse IgG (H+L, 074-1506/074-1806, Kirkegaard and Perry Laboratories, Gaithersburg, MD). Target bands were visualized by the addition of ECL Prime Western Blotting Detection Reagent (RPN2232, GE Healthcare, Hong Kong, China).…”

Section: Western Blottingmentioning

confidence: 99%

See 3 more Smart Citations

Pulmonary Silicosis Alters MicroRNA Expression in Rat Lung and miR-411-3p Exerts Anti-fibrotic Effects by Inhibiting MRTF-A/SRF Signaling

Gao

et al. 2020

Molecular Therapy - Nucleic Acids

Self Cite

View full text Add to dashboard Cite

To identify potential therapeutic targets for pulmonary fibrosis induced by silica, we studied the effects of this disease on the expression of microRNAs (miRNAs) in the lung. Rattus norvegicus pulmonary silicosis models were used in conjunction with high-throughput screening of lung specimens to compare the expression of miRNAs in control and pulmonary silicosis tissues. A total of 70 miRNAs were found to be differentially expressed between control and pulmonary silicosis tissues. This included 41 miRNAs that were upregulated and 29 that were downregulated relative to controls. Among them, miR-292-5p, miR-155-3p, miR-1193-3p, miR-411-3p, miR-370-3p, and miR-409a-5p were found to be similarly altered in rat lung and transforming growth factor (TGF)-b1-induced cultured fibroblasts. Using miRNA mimics and inhibitors, we found that miR-1193-3p, miR-411-3p, and miR-370-3p exhibited potent anti-fibrotic effects, while miR-292-5p demonstrated profibrotic effects in TGF-b1-stimulated lung fibroblasts. Moreover, we also found that miR-411-3p effectively reduced pulmonary silicosis in the mouse lung by regulating Mrtfa expression, as demonstrated using biochemical and histological assays. In conclusion, our findings indicate that miRNA expression is perturbed in pulmonary silicosis and suggest that therapeutic interventions targeting specific miRNAs might be effective in the treatment of this occupational disease.

show abstract

Section: Silicosis Alters Mirna Expression In the Rat Lungmentioning

confidence: 99%

Section: Histology and Immunostainingmentioning

confidence: 99%

Section: Histology and Immunostainingmentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

See 2 more Smart Citations

Pulmonary Silicosis Alters MicroRNA Expression in Rat Lung and miR-411-3p Exerts Anti-fibrotic Effects by Inhibiting MRTF-A/SRF Signaling

Gao

et al. 2020

Molecular Therapy - Nucleic Acids

Self Cite

View full text Add to dashboard Cite

show abstract

“…Rats were housed in SPF conditions with a daily light/dark cycle of 12 h light and 12 h darkness. Water and a standard laboratory diet were given ad libitum [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

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

Mao

Yang

Yin

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Glycolytic reprogramming is an important metabolic feature in the development of pulmonary fibrosis. However, the specific mechanism of glycolysis in silicosis is still not clear. In this study, silicotic models and silica-induced macrophage were used to elucidate the mechanism of glycolysis induced by silica. Expression levels of the key enzymes in glycolysis and macrophage activation indicators were analyzed by Western blot, qRT-PCR, IHC, and IF analyses, and by using a lactate assay kit. We found that silica promotes the expression of the key glycolysis enzymes HK2, PKM2, LDHA, and macrophage activation factors iNOS, TNF-α, Arg-1, IL-10, and MCP1 in silicotic rats and silica-induced NR8383 macrophages. The enhancement of glycolysis and macrophage activation induced by silica was reduced by Ac-SDKP or siRNA-Ldha treatment. This study suggests that Ac-SDKP treatment can inhibit glycolytic reprogramming in silica-induced lung macrophages and silicosis.

show abstract

Ac-SDKP promotes KIF3A-mediated β-catenin suppression through a ciliary mechanism to constrain silica-induced epithelial-myofibroblast transition

Liu,

Jin,

Zheng

et al. 2023

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

Silica Perturbs Primary Cilia and Causes Myofibroblast Differentiation during Silicosis by Reduction of the KIF3A-Repressor GLI3 Complex

Cited by 14 publications

References 34 publications

Pulmonary Silicosis Alters MicroRNA Expression in Rat Lung and miR-411-3p Exerts Anti-fibrotic Effects by Inhibiting MRTF-A/SRF Signaling

Pulmonary Silicosis Alters MicroRNA Expression in Rat Lung and miR-411-3p Exerts Anti-fibrotic Effects by Inhibiting MRTF-A/SRF Signaling

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

Ac-SDKP promotes KIF3A-mediated β-catenin suppression through a ciliary mechanism to constrain silica-induced epithelial-myofibroblast transition

Contact Info

Product

Resources

About