Expression of liver X receptors and protein phosphatase 1A and their relationship with airway remodeling in bronchial asthma patients_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZHENG Lin ¹ , WANG Li ² , MAO Shan ² , ZHOU Danyang ² , GU Wei ² ,  SHI Ying ²

1. Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P. R. China;
2. Department of Respiratory and Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P. R. China;

Corresponding author：

SHI Ying, Email: sykxss@163.com

Keywords：

Asthma; Liver X receptors; Protein phosphatase 1A

DOI：

10.7507/1671-6205.201905031

Video：

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Objective To detect the expression of Liver X receptors (LXRs), protein phosphatase 1A (PPM1A), transforming growth factor-β₁ (TGF-β₁) and Smad2 in peripheral blood of bronchial asthma patients, and to explore whether LXRs and PPM1A are related to airway remodeling.Methods Subjects were divided into healthy control group, mild and moderate asthma group and severe asthma group, with 30 subjects each. Lung function and high-resolution computed tomography examination were performed on patients with bronchial asthma to define airway remodeling. Peripheral blood was extracted and the serum levels of LXRα, LXRβ, PPM1A, TGF-β₁ and Smad2 were detected after centrifugation. Then the data were analyzed.Results The airway remodeling level of the mild and moderate asthma group was significantly higher than that of the control group. The airway remodeling level of the severe asthma group was significantly higher than that of the mild and moderate asthma group. Serum LXRα, LXRβ in asthma group were higher than those in the control group. The levels of LXRα and LXRβ in severe asthma were higher than those in mild and moderate asthma group. There was no significant correlation between LXRs and airway remodeling. The PPM1A level in mild and moderate asthma group was lower than that in the control group. The levels of PPM1A in severe asthma were lower than that in mild and moderate asthma group. PPM1A level was negatively correlated with airway remodeling.Conclusions The level of PPM1A in asthma patients is lower than that in healthy subjects, and is negatively correlated with the degree of airway remodeling. Serum LXRs in asthmatic patients are higher than that in healthy subjects, but LXRs are not significantly correlated with airway remodeling.

Citation： ZHENG Lin, WANG Li, MAO Shan, ZHOU Danyang, GU Wei, SHI Ying. Expression of liver X receptors and protein phosphatase 1A and their relationship with airway remodeling in bronchial asthma patients. Chinese Journal of Respiratory and Critical Care Medicine, 2020, 19(3): 229-233. doi: 10.7507/1671-6205.201905031 Copy

1.	Nunes C, Pereira AM, Morais-Almeida M. Asthma costs and social impact. Asthma Res Pract, 2017, 3: 1.
2.	Malmström K, Pelkonen AS, Mäkelä MJ. Remodeling, inflammation and airway responsiveness in early childhood asthma. Curr Opin Allergy Clin Immunol, 2013, 13(2): 203-210.
3.	Fehrenbach H, Wagner C, Wegmann M. Airway remodeling in asthma: what really matters. Cell Tissue Res, 2017, 367(3): 551-569.
4.	Ojiaku CA, Yoo EJ, Panettieri RA Jr. TGF-β1 function in airway remodeling and hyperresponsiveness: the missing link?. Am J Respir Cell Mol Biol, 2017, 56(4): 432-442.
5.	Brillet PY, Debray MP, Golmard JL, et al. Computed tomography assessment of airways throughout bronchial tree demonstrates airway narrowing in severe asthma. Acad Radiol, 2015, 22(6): 734-742.
6.	Wang J, Tucker-Kellogg L, Ng IC, et al. The self-limiting dynamics of TGF-β signaling in silico and in vitro, with negative feedback through PPM1A upregulation. PLoS Comput Biol, 2014, 10(6): e1003573.
7.	Geng J, Fan J, Ouyang Q, et al. Loss of PPM1A expression enhances invasion and the epithelial-to-mesenchymal transition in bladder cancer by activating the TGF-β/Smad signaling pathway. Oncotarget, 2014, 5(14): 5700-5711.
8.	史莹, 殷凯生, 孙丽华, 等. 肝 X 受体对支气管上皮细胞中 TGF-β1 生物功能的影响. 临床误诊误治, 2012, 25(12): 25-28.
9.	Mo J, Fang SJ, Chen W, et al. Regulation of ALK-1 signaling by the nuclear receptor LXRβ. J Biol Chem, 2002, 277(52): 50788-50794.
10.	中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南 (2016 年版). 中华结核和呼吸杂志, 2016, 39(9): 675-697.
11.	Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention (updated 2015)[EB/OL]. [2015-04-15]. http://www.ginasthma.org.
12.	中华医学会呼吸病分会慢性阻塞性肺部疾病学组. 慢性阻塞性肺疾病诊治指南 (2013 年修订版). 中华结核和呼吸杂志, 2013, 36(4): 255-264.
13.	MR Zeidler, Kleerup EC, Kim H, et al. Correlations between air trapping on HRCT and asthma symptoms in mild asthmatics. Am J Respir Crit Care Med, 2009, 179: A1268.
14.	Lin X, Duan XY, Liang YY, et al. PPM1A functions as a Smad phosphatase to terminate TGFβ signaling. Cell, 2006, 125(5): 915-928.
15.	任敦强, 刘明, 郭永忠, 等. 肝 X 受体激动剂 T0901317 抑制 TGF-β1 诱导的人正常肺成纤维细胞 α-SMA 的表达. 南方医科大学学报, 2011, 31(5): 744-748.
16.	Shi Y, Xu XT, Tan Y, et al. A liver-X-receptor ligand, T0901317, attenuates IgE production and airway remodeling in chronic asthma model of mice. PLoS One, 2014, 28: e92668.
17.	Heine G1, Dahten A, Hilt K, et al. Liver X receptors control IgE expression in B cells. J Immunol, 2009, 182(9): 5276-5282.

1. Nunes C, Pereira AM, Morais-Almeida M. Asthma costs and social impact. Asthma Res Pract, 2017, 3: 1.
2. Malmström K, Pelkonen AS, Mäkelä MJ. Remodeling, inflammation and airway responsiveness in early childhood asthma. Curr Opin Allergy Clin Immunol, 2013, 13(2): 203-210.
3. Fehrenbach H, Wagner C, Wegmann M. Airway remodeling in asthma: what really matters. Cell Tissue Res, 2017, 367(3): 551-569.
4. Ojiaku CA, Yoo EJ, Panettieri RA Jr. TGF-β1 function in airway remodeling and hyperresponsiveness: the missing link?. Am J Respir Cell Mol Biol, 2017, 56(4): 432-442.
5. Brillet PY, Debray MP, Golmard JL, et al. Computed tomography assessment of airways throughout bronchial tree demonstrates airway narrowing in severe asthma. Acad Radiol, 2015, 22(6): 734-742.
6. Wang J, Tucker-Kellogg L, Ng IC, et al. The self-limiting dynamics of TGF-β signaling in silico and in vitro, with negative feedback through PPM1A upregulation. PLoS Comput Biol, 2014, 10(6): e1003573.
7. Geng J, Fan J, Ouyang Q, et al. Loss of PPM1A expression enhances invasion and the epithelial-to-mesenchymal transition in bladder cancer by activating the TGF-β/Smad signaling pathway. Oncotarget, 2014, 5(14): 5700-5711.
8. 史莹, 殷凯生, 孙丽华, 等. 肝 X 受体对支气管上皮细胞中 TGF-β1 生物功能的影响. 临床误诊误治, 2012, 25(12): 25-28.
9. Mo J, Fang SJ, Chen W, et al. Regulation of ALK-1 signaling by the nuclear receptor LXRβ. J Biol Chem, 2002, 277(52): 50788-50794.
10. 中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南 (2016 年版). 中华结核和呼吸杂志, 2016, 39(9): 675-697.
11. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention (updated 2015)[EB/OL]. [2015-04-15]. http://www.ginasthma.org.
12. 中华医学会呼吸病分会慢性阻塞性肺部疾病学组. 慢性阻塞性肺疾病诊治指南 (2013 年修订版). 中华结核和呼吸杂志, 2013, 36(4): 255-264.
13. MR Zeidler, Kleerup EC, Kim H, et al. Correlations between air trapping on HRCT and asthma symptoms in mild asthmatics. Am J Respir Crit Care Med, 2009, 179: A1268.
14. Lin X, Duan XY, Liang YY, et al. PPM1A functions as a Smad phosphatase to terminate TGFβ signaling. Cell, 2006, 125(5): 915-928.
15. 任敦强, 刘明, 郭永忠, 等. 肝 X 受体激动剂 T0901317 抑制 TGF-β1 诱导的人正常肺成纤维细胞 α-SMA 的表达. 南方医科大学学报, 2011, 31(5): 744-748.
16. Shi Y, Xu XT, Tan Y, et al. A liver-X-receptor ligand, T0901317, attenuates IgE production and airway remodeling in chronic asthma model of mice. PLoS One, 2014, 28: e92668.
17. Heine G1, Dahten A, Hilt K, et al. Liver X receptors control IgE expression in B cells. J Immunol, 2009, 182(9): 5276-5282.

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Expression of liver X receptors and protein phosphatase 1A and their relationship with airway remodeling in bronchial asthma patients

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