Epithelial‑mesenchymal transition in chronic rhinosinusitis (CRS) and the prognostic value of α‑SMA in postoperative outcomes of patients with CRS

  • Authors:
    • Han Li
    • Quan Liu
    • Huan Wang
    • Xi‑Cai Sun
    • Hua‑Peng Yu
    • Li Hu
    • De‑Hui Wang
  • View Affiliations

  • Published online on: July 3, 2019     https://doi.org/10.3892/mmr.2019.10461
  • Pages: 2441-2449
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Abstract

Tissue remodeling is the pathological basis of the symptoms encountered in chronic rhinosinusitis (CRS). Epithelial‑mesenchymal transition (EMT) may participate in this process. The present study was designed to investigate the involvement of EMT in CRS. In addition, the prognostic value of the EMT biomarker α‑smooth muscle actin (α‑SMA) was assessed in patients with CRS who underwent endoscopic sinus surgery (ESS). A total of 13 patients with CRS without nasal polyps (CRSsNP), 13 patients with CRS with nasal polyps (CRSwNP) and 13 control subjects were enrolled. The expression of EMT markers was determined in sinonasal specimens by qPCR, western blot and immunofluorescence assays. EMT features were evaluated in primary nasal epithelial cells (NECs) with transforming growth factor (TGF)‑β1 stimulation. The associations were assessed between α‑SMA expression and the clinical features of CRS. Epithelial and mesenchymal markers were overexpressed in the sinonasal specimens of both CRSsNP and CRSwNP patients. Alterations in the expression pattern were more apparent in the CRSsNP patients. Following incubation of primary NECs with TGF‑β1, a mesenchymal shape was acquired. In addition, NECs that co‑expressed α‑SMA and cytokeratin were readily detected and the protein levels of α‑SMA were elevated. In contrast to α‑SMA, the levels of E‑cadherin were decreased. The protein levels of α‑SMA were negatively correlated with endoscopic scores and several postoperative symptoms. In conclusion, partial EMT occurred in patients with CRS, notably in CRSsNP patients. Moreover, primary NECs could undergo EMT following TGF‑β1 treatment in vitro. In addition, α‑SMA could be considered an efficient predictor for postoperative endoscopic and symptomatic outcomes in patients with CRS treated with ESS.

References

1 

Bhattacharyya N and Gilani S: Prevalence of potential adult chronic rhinosinusitis symptoms in the United States. Otolaryngol Head Neck Surg. 159:522–525. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Shi JB, Fu QL, Zhang H, Cheng L, Wang YJ, Zhu DD, Lv W, Liu SX, Li PZ, Ou CQ and Xu G: Epidemiology of chronic rhinosinusitis: Results from a cross-sectional survey in seven Chinese cities. Allergy. 70:533–539. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Lee JM, Dedhar S, Kalluri R and Thompson EW: The epithelial-mesenchymal transition: New insights in signaling, development, and disease. J Cell Biol. 172:973–981. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Nieto MA, Huang RY, Jackson RA and Thiery JP: EMT: 2016. Cell. 166:21–45. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Stone RC, Pastar I, Ojeh N, Chen V, Liu S, Garzon KI and Tomic-Canic M: Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell Tissue Res. 365:495–506. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Jiang B, Guan Y, Shen HJ, Zhang LH, Jiang JX, Dong XW, Shen HH and Xie QM: Akt/PKB signaling regulates cigarette smoke-induced pulmonary epithelial-mesenchymal transition. Lung Cancer. 122:44–53. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Stasikowska-Kanicka O, Wagrowska-Danilewicz M and Danilewicz M: Immunohistochemical study EMT-related proteins in HPV-, and EBV-negative patients with sinonasal tumours. Pathol Oncol Res. 22:781–788. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Lai T, Li Y, Chen M, Pan G, Wen X, Mai Z, Yuan Y, Lv Y, Lv Q, Cen R, et al: Heparin-binding epidermal growth factor contributes to COPD disease severity by modulating airway fibrosis and pulmonary epithelial-mesenchymal transition. Lab Invest. 98:1159–1169. 2018. View Article : Google Scholar : PubMed/NCBI

9 

Sun J, Gu X, Wu N, Zhang P, Liu Y and Jiang S: Human antigen R enhances the epithelial-mesenchymal transition via regulation of ZEB-1 in the human airway epithelium. Respir Res. 19:1092018. View Article : Google Scholar : PubMed/NCBI

10 

Shin HW, Cho K, Kim DW, Han DH, Khalmuratova R, Kim SW, Jeon SY, Min YG, Lee CH, Rhee CS and Park JW: Hypoxia-inducible factor 1 mediates nasal polypogenesis by inducing epithelial-to-mesenchymal transition. Am J Respir Crit Care Med. 185:944–954. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Lee M, Kim DW, Yoon H, So D, Khalmuratova R, Rhee CS, Park JW and Shin HW: Sirtuin 1 attenuates nasal polypogenesis by suppressing epithelial-to-mesenchymal transition. J Allergy Clin Immunol. 137:87–98.e7. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Razali RA, Nik Ahmad Eid NAH, Jayaraman T, Amir Hassan MA, Azlan NQ, Ismail NF, Sainik N, Yazid MD, Lokanathan Y, Saim AB and Hj Idrus RB: The potential of Olea europaea extracts to prevent TGFβ1-induced epithelial to mesenchymal transition in human nasal respiratory epithelial cells. BMC Complement Altern Med. 18:1972018. View Article : Google Scholar : PubMed/NCBI

13 

Yang HW, Lee SA, Shin JM, Park IH and Lee HM: Glucocorticoids ameliorate TGF-β1-mediated epithelial-to-mesenchymal transition of airway epithelium through MAPK and Snail/Slug signaling pathways. Sci Rep. 7:34862017. View Article : Google Scholar : PubMed/NCBI

14 

Park IH, Kang JH, Shin JM and Lee HM: Trichostatin A inhibits epithelial mesenchymal transition induced by TGF-β1 in Airway Epithelium. PLoS One. 11:e01620582016. View Article : Google Scholar : PubMed/NCBI

15 

Konnecke M, Burmeister M, Pries R, Boscke R, Bruchhage KL, Ungefroren H, Klimek L and Wollenberg B: Epithelial-mesenchymal transition in chronic rhinosinusitis: Differences revealed between epithelial cells from nasal polyps and inferior turbinates. Arch Immunol Ther Exp (Warsz). 65:157–173. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Hupin C, Gohy S, Bouzin C, Lecocq M, Polette M and Pilette C: Features of mesenchymal transition in the airway epithelium from chronic rhinosinusitis. Allergy. 69:1540–1549. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Fokkens W, Lund V and Mullol J; European Position Paper on Rhinosinusitis and Nasal Polyps Group, : European position paper on rhinosinusitis and nasal polyps 2007. Rhinol Suppl. 20:1–136. 2007.PubMed/NCBI

18 

Zhang L and Zhang LH: Comparison of different endoscopic scoring systems in patients with chronic rhinosinusitis: Reliability, validity, responsiveness and correlation. Rhinology. 55:363–368. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Greguric T, Trkulja V, Baudoin T, Grgic M, Smigovec I and Kalogjera L: Differences in the sino-nasal outcome test 22 and visual analog scale symptom scores in chronic rhinosinusitis with and without nasal polyps. Am J Rhinol Allergy. 30:107–112. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Dietz de Loos DA, Hopkins C and Fokkens WJ: Symptoms in chronic rhinosinusitis with and without nasal polyps. Laryngoscope. 123:57–63. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Hellquist HB: Nasal polyps update. Histopathology. Allergy Asthma Proc. 17:237–242. 1996. View Article : Google Scholar : PubMed/NCBI

23 

Sedaghat AR: Chronic Rhinosinusitis. Am Fam Physician. 96:500–506. 2017.PubMed/NCBI

24 

Campbell K: Contribution of epithelial-mesenchymal transitions to organogenesis and cancer metastasis. Curr Opin Cell Biol. 55:30–35. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Lovisa S, LeBleu VS, Tampe B, Sugimoto H, Vadnagara K, Carstens JL, Wu CC, Hagos Y, Burckhardt BC, Pentcheva-Hoang T, et al: Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis. Nat Med. 21:998–1009. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Sader F, Denis JF, Laref H and Roy S: Epithelial to mesenchymal transition is mediated by both TGF-β canonical and non-canonical signaling during axolotl limb regeneration. Sci Rep. 9:11442019. View Article : Google Scholar : PubMed/NCBI

28 

Weiss A and Attisano L: The TGFbeta superfamily signaling pathway. Wiley Interdiscip Rev Dev Biol. 2:47–63. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Darby IA, Zakuan N, Billet F and Desmoulière A: The myofibroblast, a key cell in normal and pathological tissue repair. Cell Mol Life Sci. 73:1145–1157. 2016. View Article : Google Scholar : PubMed/NCBI

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September 2019
Volume 20 Issue 3

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Copy and paste a formatted citation
APA
Li, H., Liu, Q., Wang, H., Sun, X., Yu, H., Hu, L., & Wang, D. (2019). Epithelial‑mesenchymal transition in chronic rhinosinusitis (CRS) and the prognostic value of α‑SMA in postoperative outcomes of patients with CRS. Molecular Medicine Reports, 20, 2441-2449. https://doi.org/10.3892/mmr.2019.10461
MLA
Li, H., Liu, Q., Wang, H., Sun, X., Yu, H., Hu, L., Wang, D."Epithelial‑mesenchymal transition in chronic rhinosinusitis (CRS) and the prognostic value of α‑SMA in postoperative outcomes of patients with CRS". Molecular Medicine Reports 20.3 (2019): 2441-2449.
Chicago
Li, H., Liu, Q., Wang, H., Sun, X., Yu, H., Hu, L., Wang, D."Epithelial‑mesenchymal transition in chronic rhinosinusitis (CRS) and the prognostic value of α‑SMA in postoperative outcomes of patients with CRS". Molecular Medicine Reports 20, no. 3 (2019): 2441-2449. https://doi.org/10.3892/mmr.2019.10461