Extracellular Signal-regulated Kinase Signaling Pathway and Silicosis

Overview

Journal Toxicol Res (Camb)

Publisher Oxford University Press

Date 2021 Jun 18

PMID 34141162

Citations 5

Authors

Yujia Xie

Jixuan Ma

Meng Yang

Lieyang Fan

Weihong Chen

Affiliations

Soon will be listed here.

Abstract

Silicosis is a scarring lung disease caused by inhaling fine particles of crystalline silica in the workplace of many industries. Due to the lack of effective treatment and management, the continued high incidence of silicosis remains a major public health concern worldwide, especially in the developing countries. Till now, related molecular mechanisms underlying silicosis are still not completely understood. Multiple pathways have been reported to be participated in the pathological process of silicosis, and more complex signaling pathways are receiving attention. The activated extracellular signal-regulated kinase (ERK) signaling pathway has been recognized to control some functions in the cell. Recent studies have identified that the ERK signaling pathway contributes to the formation and development of silicosis through regulating the processes of oxidative stress, inflammatory response, proliferation and activation of fibroblasts, epithelial-mesenchymal transformation, autophagy, and apoptosis of cells. In this review article, we summarize the latest findings on the role of ERK signaling pathway in silica-induced experimental models of silicosis, as well as clinical perspectives.

Citing Articles

The role of inflammation in silicosis.

Liu T, Sun H, Han Y, Zhan Y, Jiang J Front Pharmacol. 2024; 15:1362509.

PMID: 38515835 PMC: 10955140. DOI: 10.3389/fphar.2024.1362509.

Fermented cordyceps powder alleviates silica-induced pulmonary inflammation and fibrosis in rats by regulating the Th immune response.

Pu S, Yang Z, Zhang X, Li M, Han N, Yang X Chin Med. 2023; 18(1):131.

PMID: 37828528 PMC: 10571334. DOI: 10.1186/s13020-023-00823-8.

From Basic Research to Clinical Practice: Considerations for Treatment Drugs for Silicosis.

Li R, Kang H, Chen S Int J Mol Sci. 2023; 24(9).

PMID: 37176040 PMC: 10179659. DOI: 10.3390/ijms24098333.

LPAR5 confers radioresistance to cancer cells associated with EMT activation via the ERK/Snail pathway.

Sun X, Li H, Xie D, Gao S, Huang X, Guan H J Transl Med. 2022; 20(1):456.

PMID: 36199069 PMC: 9533496. DOI: 10.1186/s12967-022-03673-4.

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling.

Cheng D, Xu Q, Wang Y, Li G, Sun W, Ma D J Transl Med. 2021; 19(1):349.

PMID: 34399790 PMC: 8365894. DOI: 10.1186/s12967-021-03036-5.

References

t Mannetje A, Steenland K, ATTFIELD M, Boffetta P, Checkoway H, Deklerk N . Exposure-response analysis and risk assessment for silica and silicosis mortality in a pooled analysis of six cohorts. Occup Environ Med. 2002; 59(11):723-8. PMC: 1740236. DOI: 10.1136/oem.59.11.723. View

Cagnol S, Chambard J . ERK and cell death: mechanisms of ERK-induced cell death--apoptosis, autophagy and senescence. FEBS J. 2009; 277(1):2-21. DOI: 10.1111/j.1742-4658.2009.07366.x. View

Ng B, Dong J, Viswanathan S, Widjaja A, Paleja B, Adami E . Fibroblast-specific IL11 signaling drives chronic inflammation in murine fibrotic lung disease. FASEB J. 2020; 34(9):11802-11815. DOI: 10.1096/fj.202001045RR. View

Nardi J, Nascimento S, Goethel G, Gauer B, Sauer E, Fao N . Inflammatory and oxidative stress parameters as potential early biomarkers for silicosis. Clin Chim Acta. 2018; 484:305-313. DOI: 10.1016/j.cca.2018.05.045. View

Li W, Xie L, Ma J, Yang M, Wang B, Xu Y . Genetic loss of Gas6/Mer pathway attenuates silica-induced lung inflammation and fibrosis in mice. Toxicol Lett. 2019; 313:178-187. DOI: 10.1016/j.toxlet.2019.07.008. View

Ng B, Dong J, DAgostino G, Viswanathan S, Widjaja A, Lim W . Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Sci Transl Med. 2019; 11(511). DOI: 10.1126/scitranslmed.aaw1237. View

Bhattacharyya S, Wu M, Fang F, Tourtellotte W, Feghali-Bostwick C, Varga J . Early growth response transcription factors: key mediators of fibrosis and novel targets for anti-fibrotic therapy. Matrix Biol. 2011; 30(4):235-42. PMC: 3135176. DOI: 10.1016/j.matbio.2011.03.005. View

Rout-Pitt N, Farrow N, Parsons D, Donnelley M . Epithelial mesenchymal transition (EMT): a universal process in lung diseases with implications for cystic fibrosis pathophysiology. Respir Res. 2018; 19(1):136. PMC: 6052671. DOI: 10.1186/s12931-018-0834-8. View

Mossman B, Churg A . Mechanisms in the pathogenesis of asbestosis and silicosis. Am J Respir Crit Care Med. 1998; 157(5 Pt 1):1666-80. DOI: 10.1164/ajrccm.157.5.9707141. View

10.

Yan W, Xiaoli L, Guoliang A, Zhonghui Z, Di L, Ximeng L . SB203580 inhibits epithelial-mesenchymal transition and pulmonary fibrosis in a rat silicosis model. Toxicol Lett. 2016; 259:28-34. DOI: 10.1016/j.toxlet.2016.07.591. View

11.

Liu H, Cheng Y, Yang J, Wang W, Fang S, Zhang W . BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis. Cell Death Dis. 2017; 8(3):e2657. PMC: 5386570. DOI: 10.1038/cddis.2017.78. View

12.

Nemeth A, Mozes M, Calvier L, Hansmann G, Kokeny G . The PPARγ agonist pioglitazone prevents TGF-β induced renal fibrosis by repressing EGR-1 and STAT3. BMC Nephrol. 2019; 20(1):245. PMC: 6610924. DOI: 10.1186/s12882-019-1431-x. View

13.

Lavoie H, Therrien M . Regulation of RAF protein kinases in ERK signalling. Nat Rev Mol Cell Biol. 2015; 16(5):281-98. DOI: 10.1038/nrm3979. View

14.

Jimenez L, Zanella C, Fung H, Janssen Y, Vacek P, Charland C . Role of extracellular signal-regulated protein kinases in apoptosis by asbestos and H2O2. Am J Physiol. 1997; 273(5):L1029-35. DOI: 10.1152/ajplung.1997.273.5.L1029. View

15.

Boucherat O, Landry-Truchon K, Aoidi R, Houde N, Nadeau V, Charron J . Lung development requires an active ERK/MAPK pathway in the lung mesenchyme. Dev Dyn. 2016; 246(1):72-82. DOI: 10.1002/dvdy.24464. View

16.

Ovrevik J, Lag M, Schwarze P, Refsnes M . p38 and Src-ERK1/2 pathways regulate crystalline silica-induced chemokine release in pulmonary epithelial cells. Toxicol Sci. 2004; 81(2):480-90. DOI: 10.1093/toxsci/kfh214. View

17.

Tomaru M, Matsuoka M . The role of mitogen-activated protein kinases in crystalline silica-induced cyclooxygenase-2 expression in A549 human lung epithelial cells. Toxicol Mech Methods. 2011; 21(7):513-9. DOI: 10.3109/15376516.2011.568982. View

18.

Antognelli C, Gambelunghe A, Muzi G, Talesa V . Peroxynitrite-mediated glyoxalase I epigenetic inhibition drives apoptosis in airway epithelial cells exposed to crystalline silica via a novel mechanism involving argpyrimidine-modified Hsp70, JNK, and NF-κB. Free Radic Biol Med. 2015; 84:128-141. DOI: 10.1016/j.freeradbiomed.2015.03.026. View

19.

Cho Y, Seo M, Kim J, Lim Y, Chae G, Ha K . Silica-induced generation of reactive oxygen species in Rat2 fibroblast: role in activation of mitogen-activated protein kinase. Biochem Biophys Res Commun. 1999; 262(3):708-12. DOI: 10.1006/bbrc.1999.1274. View

20.

Li D, Hu J, Wang T, Zhang X, Liu L, Wang H . Silymarin attenuates cigarette smoke extract-induced inflammation via simultaneous inhibition of autophagy and ERK/p38 MAPK pathway in human bronchial epithelial cells. Sci Rep. 2016; 6:37751. PMC: 5118787. DOI: 10.1038/srep37751. View