Skip to main content
Log in

Sox9 protects against human lung fibroblast cell apoptosis induced by LPS through activation of the AKT/GSK3β pathway

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

An EDITORIAL EXPRESSION OF CONCERN to this article was published on 20 October 2021

This article has been updated

Abstract

Sex-determining region Y-box 9 (Sox9) is an important transcription factor that has been identified as a key regulator of several types of diseases. In this study, we explored the correlation of Sox9 with cell proliferation, apoptosis, inflammatory factor expression, and the possible signaling pathway in human lung fibroblast cell line to investigate the possible mechanism of neonatal pneumonia. Therefore, in the present study, pc-Sox9 and si-Sox9 were transfected into MRC-5 (human fetal lung fibroblast cell line) to promote or inhibit expression of Sox-9. Quantitative reverse-transcription polymerase chain reaction and Western blot were used to determine the expression level of Sox-9 at mRNA and protein level. Then 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and flow cytometry were used to explore, respectively, proliferation and apoptosis in vitro. We found that Sox9 could significantly upregulate the proliferation rate and inhibit apoptosis rate and inflammatory factor expression of MRC-5 cells compared with a control group. Moreover, the signaling pathway study confirmed that Sox9 protected MRC-5 from lipopolysaccharide injury through the AKT/GSK3β pathway. All these findings suggest that Sox9 acts as a novel marker for neonatal pneumonia and could be a new therapeutic target for this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Change history

Abbreviations

AKT:

serine/threonine kinase (also known as PKB, protein kinase B)

GSK3β:

glycogen synthase kinase-3β

LPS:

lipopolysaccharide

MRC-5:

human fetal lung fibroblast cell line

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (assay)

Sox9:

sex-determining region Y-box 9

References

  1. Cernada, M., Aguar, M., Brugada, M., Gutierrez, A., Lopez, J. L., Castell, M., and Vento, M. (2013) Ventilatorassociated pneumonia in newborn infants diagnosed with an invasive bronchoalveolar lavage technique: a prospective observational study, Pediatr. Crit. Care Med., 14, 55–61.

    Article  PubMed  Google Scholar 

  2. Elnadi, N. A., Almasry, A. E., and Abosdera, M. M. (2013) Prevalence and effect of a combined treatment on pneumocystitis pneumonia, J. Egypt. Soc. Parasitol., 43, 457–462.

    Article  PubMed  Google Scholar 

  3. Vissing, N. H., Chawes, B. L., and Bisgaard, H. (2013) Increased risk of pneumonia and bronchiolitis after bacterial colonization of the airways as neonates, Am. J. Respir. Crit. Care Med., 188, 1246–1252.

    Article  PubMed  Google Scholar 

  4. Zhang, D. S., Chen, C., Zhou, W., Yao, and Chen, Y. J. (2013) The risk factors of ventilatorassociated pneumonia in newborn and the changes of isolated pathogens, Sichuan Da Xue Xue Bao Yi Xue Ban, 44, 584–587.

    PubMed  Google Scholar 

  5. Zar, H. J., Barnett, W., Myer, L., and Nicol, M. P. (2016) Childhood pneumonia–the Drakenstein Child Health Study, S. Afr. Med. J., 106, 642–643.

    Article  PubMed  Google Scholar 

  6. Roux, D. M. L., Myer, L., Nicol, M. P., and Zar, H. J. (1969) Incidence and severity of childhood pneumonia in the first year of life in a South African birth cohort: the Drakenstein Child Health Study, Lancet Glob. Health, 3, e95–e103.

    Article  Google Scholar 

  7. Chisti, M. J., Salam, M. A., Smith, J. H., Ahmed, T., Ashraf, H., Bardhan, P. K., and Pietroni, M. A. C. (2011) Impact of lack of breast feeding during neonatal age on the development of clinical signs of pneumonia and hypoxemia in young infants with diarrhea, Plos One, 6, e25817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Shu, L. H., Jiang-Jiang, X. U., Wang, S., Zhong, H. Q., Dong, X. Y., Jiang, K., Zhang, H. Y., Xiong, Q., Wang, C., and Sun, T. (2015) Distribution of pathogenic microorganisms and its relationship with clinical features in children with communityacquired pneumonia, Zhongguo Dang Dai Er Ke Za Zhi, 17, 1056–1061.

    PubMed  Google Scholar 

  9. Peng, C. C., Wu, S. J., Chen, M. R., Chiu, N. C., and Chi, H. (2012) Clinical experience of extracorporeal membrane oxygenation for acute respiratory distress syndrome associated with pneumonia in children, J. Formos. Med. Assoc., 111, 147–152.

    Article  PubMed  Google Scholar 

  10. Stockl, S., Bauer, R. J., Bosserhoff, A. K., Gottl, C., Grifka, J., and Grassel, S. (2013) Sox9 modulates cell survival and adipogenic differentiation of multipotent adult rat mesenchymal stem cells, J. Cell Sci., 126, 2890–2902.

    Article  PubMed  Google Scholar 

  11. Mccoy, J. A., Hamlin, H. J., Thayer, L. A., Guillette, L. J., and Parrott, B. B. (2016) The influence of thermal signals during embryonic development on intrasexual and sexually dimorphic gene expression and circulating steroid hormones in American alligator hatchlings (Alligator mississippiensis), Gen. Comp. Endocrinol., 104, 9919–9924.

    Google Scholar 

  12. Kim, G. J., Sock, E., Buchberger, A., Just, W., Denzer, F., Hoepffner, W., German, J., Cole, T., Mann, J., and Seguin, J. H. (2015) Copy number variation of two separate regulatory regions upstream of SOX9 causes isolated 46,XY or 46,XX disorder of sex development, J. Med. Genet., 52, 240–247.

    Article  CAS  PubMed  Google Scholar 

  13. Oh, C., Yasuda, H., Henry, S., Zhang, Z., Xue, M., De Crombrugghe, B. D., and Chen, D. (2016) SOX9 directly regulates CTGF/CCN2 transcription in growth plate chondrocytes and in nucleus pulposus cells of intervertebral disc, Sci. Rep., 6, 29916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu, C., Liu, L., Chen, X., Cheng, J., Zhang, H., Shen, J., Shan, J., Xu, Y., Yang, Z., and Lai, M. (2016) Sox9 regulates selfrenewal and tumorigenicity by promoting symmetrical cell division of cancer stem cells in hepatocellular carcinoma, Hepatology, 64, 117–129.

    Article  CAS  PubMed  Google Scholar 

  15. Ma, F., Ye, H., He, H. H., Gerrin, S. J., Chen, S., Tanenbaum, B. A., Cai, C., Sowalsky, A. G., He, L., and Wang, H. (2016) SOX9 drives WNT pathway activation in prostate cancer, J. Clin. Invest., 126, 1745–1758.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Prevostel, C., Rammah-Bouazza, C., Trauchessec, H., Canterel-Thouennon, L., Busson, M., Ychou, M., and Blache, P. (2016) SOX9 is an atypical intestinal tumor suppressor controlling the oncogenic Wnt/β-catenin signaling, Oncotarget, 7, 82228–82243.

    PubMed  PubMed Central  Google Scholar 

  17. Petrache Voicu, S. N., Dinu, D., Sima, C., Hermenean, A., Ardelean, A., Codrici, E., Stan, M. S., Zarnescu, O., and Dinischiotu, A. (2015) Silica nanoparticles induce oxidative stress and autophagy but not apoptosis in the MRC-5 cell line, Int. J. Mol. Sci., 16, 29398–29416.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Giulia, B., Luisa, A., Concetta, S., Bruna, L. S., Chiara, B., and Marcello, C. (2015) Procalcitonin and communityacquired pneumonia (CAP) in children, Clin. Chim. Acta, 451, 215–218.

    Article  CAS  PubMed  Google Scholar 

  19. Wang, H. J., Shi, H., Zhou, W., Zheng-Qiang, H. U., Li-Yuan, M. U., and Min, S. U. (2012) Common pathogens and clinical characteristics of neonatal pneumonia, Zhongguo Dang Dai Er Ke Za Zhi., 14, 898–902.

    CAS  PubMed  Google Scholar 

  20. Kumar, S., Jing, L., Pang, P., Krautzberger, A. M., Reginensi, A., Akiyama, H., Schedl, A., Humphreys, B., and Mcmahon, A. (2015) Sox9 activation highlights a cellular pathway of renal repair in the acutely injured mammalian kidney, Cell Rep., 12, 1325–1338.

    Article  CAS  PubMed  Google Scholar 

  21. Wang, H. Y., Lian, P., and Zheng, P. S. (2015) SOX9, a potential tumor suppressor in cervical cancer, transactivates p21WAF1/CIP1 and suppresses cervical tumor growth, Oncotarget, 6, 20711–20722.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hong, Y., Chen, W., Du, X., Ning, H., Chen, H., Shi, R., Lin, S., Xu, R., Zhu, J., and Wu, S. (2015) Upregulation of sexdetermining region Y-box 9 (SOX9) promotes cell proliferation and tumorigenicity in esophageal squamous cell carcinoma, Oncotarget, 6, 31241–31254.

    PubMed  PubMed Central  Google Scholar 

  23. Li, L., Zhang, H., Min, D., Zhang, R., Wu, J., Qu, H., and Tang, Y. (2015) Sox9 activation is essential for the recovery of lung function after acute lung injury, Cell. Physiol. Biochem., 37, 1113–1122.

    Article  CAS  PubMed  Google Scholar 

  24. Li, J., Wang, L., Liu, Z., Chao, Z., Xing, F., Pei, Y., Yang, Y., Dang, X., and Wang, K. (2015) MicroRNA-494 inhibits cell proliferation and invasion of chondrosarcoma cells in vivo and in vitro by directly targeting SOX9, Oncotarget, 6, 26216–26229.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wang, Z., Liang, D. C., Bai, J. Y., Kang, N., Feng, J. Y., and Yang, Z. Q. (2015) Overexpression of Sox9 gene by the lentiviral vector in rabbit bone marrow mesenchymal stem cells for promoting the repair of cartilage defect, Zhongguo Gu Shang, 28, 433–440.

    PubMed  Google Scholar 

  26. Jin, D., Qian, C., Su, M., Chen, M., and Jie, C. (2016) Gastrokine-2 suppresses epithelial mesenchymal transition through PI3K/AKT/GSK3β signaling in gastric cancer, Tumor Biol., 37, 12403–12410.

    Article  Google Scholar 

  27. Zhu, M., Li, J., Wang, K., Hao, X., Ge, R., and Li, Q. (2016) Isoquercitrin inhibits hydrogen peroxideinduced apoptosis of EA.hy926 cells via the PI3K/Akt/GSK3β signaling pathway, Molecules, 21, 356.

    Article  PubMed  Google Scholar 

  28. Jie, F., Sun, Q., Lei, L., and Da, X. (2015) Photoactivation of TAZ via Akt/GSK3β signaling pathway promotes osteogenic differentiation, Int. J. Biochem. Cell Biol., 66, 59–68.

    Article  Google Scholar 

  29. Cernada, M., Brugada, M., Golombek, S., and Vento, M. (2014) Ventilatorassociated pneumonia in neonatal patients: an update, Neonatology, 105, 98–107.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tao Wang.

Additional information

Published in Russian in Biokhimiya, 2017, Vol. 82, No. 5, pp. 808-816.

To whom correspondence should be addressed.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhu, Z., Dai, J., Liao, Y. et al. Sox9 protects against human lung fibroblast cell apoptosis induced by LPS through activation of the AKT/GSK3β pathway. Biochemistry Moscow 82, 606–612 (2017). https://doi.org/10.1134/S000629791705008X

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S000629791705008X

Keywords

Navigation