The mechanism of Wnt5a and its receptor in bronchiectasis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LIU Bicui ^1,2 , QIN Shihe ³ , YANG Hua ³ ,  LIU Chuntao ¹

1. Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Respiratory and Critical Care Medicine, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing 402760, P. R. China;
3. Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of Hubei Minzu University, Enshi, Hubei 445000, P. R. China;

Corresponding author：

LIU Chuntao, Email: taosen666999@163.com

Keywords：

Bronchiectasis; Wnt5a; mechanism

DOI：

10.7507/1671-6205.202210016

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Objective To explore the potential roles and mechanism of Wnt5a and its receptors in the pathogenesis of bronchiectasis. Methods From October 2017 to April 2018, outpatients with bronchiectasis who needed bronchoscopy were recruited in the Department of Respiratory and Critical Care Medicine of West China Hospital of Sichuan University. The control group was patients with pulmonary nodules less than 10 mm in diameter by health inspection. Patients who used antibiotics and/or glucocorticoids within the past 4 weeks or had other airway diseases were excluded. Serum and bronchial mucosa were collected for detection of Wnt5a by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR), respectively. The receptor of Wnt5a, Ror2, and the downstream pro-inflammatory cytokines, interleukin (IL)-1β and IL-6, were measured in the bronchial mucosa by real-time PCR. Results From October 2017 to April 2018, 32 outpatients with bronchiectasis were found but only 17 patients finished this study, and simultaneously 18 patients with pulmonary nodules were chosen as control. The level of serum Wnt5a in patients with bronchiectasis were significantly higher than that in the control group (P<0.05). Correlation analyses showed that serum Wnt5a level was positively correlated with the level of serum C reactive protein (r=0.806, P<0.05), but had no relation with the level of white blood cell count, blood neutrophil percentage, pulmonary function or bronchiectasis severe index. The mRNA levels of Wnt5a and its receptor Ror2 in bronchial mucosa of patients with bronchiectasis were significantly higher than those in the control group (P<0.001). The mRNA levels of IL-1β and IL-6 in bronchial mucosa of patients with bronchiectasis were higher than those in the control group (P<0.05). Conclusion Wnt5a may play crucial roles in the development of bronchiectasis through Wnt5a/Ror2 signaling pathways to regulate the release of pro-inflammatory cytokines including IL-1β and IL-6.

Citation： LIU Bicui, QIN Shihe, YANG Hua, LIU Chuntao. The mechanism of Wnt5a and its receptor in bronchiectasis. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(11): 768-772. doi: 10.7507/1671-6205.202210016 Copy

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2.	Chalmers JD, Aliberti S, Blasi F. Management of bronchiectasis in adults. Eur Respir J, 2015, 45(5): 1446-1462.
3.	Pashirzad M, Shafiee M, Rahmani F, et al. Role of Wnt5a in the pathogenesis of inflammatory diseases. J Cell Physiol, 2017, 232(7): 1611-1616.
4.	Pereira C, Schaer DJ, Bachli EB, et al. Wnt5A/CaMKII signaling contributes to the inflammatory response of macrophages and is a target for the antiinflammatory action of activated protein C and interleukin-10. Arterioscler Thromb Vasc Biol, 2008, 28(3): 504-510.
5.	Schulte DM, Kragelund D, Müller N, et al. The wingless-related integration site-5a/secreted frizzled-related protein-5 system is dysregulated in human sepsis. Clin Exp Immunol, 2015, 180(1): 90-97.
6.	祁俊, 胡克苏, 张逸, 等. 烧伤脓毒症患者早期血清Wnt5a的变化及意义. 贵州医药, 2015, 39(1): 55-57.
7.	McShane PJ, Naureckas ET, Tino G, et al. Non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med, 2013, 188(6): 647-656.
8.	Reiff DB, Wells AU, Carr DH, et al. CT findings in bronchiectasis: limited value in distinguishing between idiopathic and specific types. Am J Roentgenol, 1995, 165(2): 261-267.
9.	Green JL, Kuntz SG, Sternberg PW. Ror receptor tyrosine kinases: orphans no more. Trends Cell Biol, 2008, 18(11): 536-544.
10.	Nishita M, Itsukushima S, Nomachi A, et al. Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization. Mol Cell Biol, 2010, 30(14): 3610-3619.
11.	Oishi I, Suzuki H, Onishi N, et al. The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells, 2003, 8(7): 645-554.
12.	Mikels A, Minami Y, Nusse R. Ror2 receptor requires tyrosine kinase activity to mediate Wnt5A signaling. J Biol Chem, 2009, 284(44): 30167-30176.
13.	刘征, 吴洪涛, 倪亚光, 等. Wnt5a与炎症信号在炎症性疾病中的交叉互动. 生理学报, 2009, 284(44): 30167-30176.

1. Polverino E, Goeminne PC, McDonnell MJ, et al. European Respiratory Society Guidelines for the Management of Adult Bronchiectasis. Eur Respir J, 2017, 50(3): 1700629.
2. Chalmers JD, Aliberti S, Blasi F. Management of bronchiectasis in adults. Eur Respir J, 2015, 45(5): 1446-1462.
3. Pashirzad M, Shafiee M, Rahmani F, et al. Role of Wnt5a in the pathogenesis of inflammatory diseases. J Cell Physiol, 2017, 232(7): 1611-1616.
4. Pereira C, Schaer DJ, Bachli EB, et al. Wnt5A/CaMKII signaling contributes to the inflammatory response of macrophages and is a target for the antiinflammatory action of activated protein C and interleukin-10. Arterioscler Thromb Vasc Biol, 2008, 28(3): 504-510.
5. Schulte DM, Kragelund D, Müller N, et al. The wingless-related integration site-5a/secreted frizzled-related protein-5 system is dysregulated in human sepsis. Clin Exp Immunol, 2015, 180(1): 90-97.
6. 祁俊, 胡克苏, 张逸, 等. 烧伤脓毒症患者早期血清Wnt5a的变化及意义. 贵州医药, 2015, 39(1): 55-57.
7. McShane PJ, Naureckas ET, Tino G, et al. Non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med, 2013, 188(6): 647-656.
8. Reiff DB, Wells AU, Carr DH, et al. CT findings in bronchiectasis: limited value in distinguishing between idiopathic and specific types. Am J Roentgenol, 1995, 165(2): 261-267.
9. Green JL, Kuntz SG, Sternberg PW. Ror receptor tyrosine kinases: orphans no more. Trends Cell Biol, 2008, 18(11): 536-544.
10. Nishita M, Itsukushima S, Nomachi A, et al. Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization. Mol Cell Biol, 2010, 30(14): 3610-3619.
11. Oishi I, Suzuki H, Onishi N, et al. The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells, 2003, 8(7): 645-554.
12. Mikels A, Minami Y, Nusse R. Ror2 receptor requires tyrosine kinase activity to mediate Wnt5A signaling. J Biol Chem, 2009, 284(44): 30167-30176.
13. 刘征, 吴洪涛, 倪亚光, 等. Wnt5a与炎症信号在炎症性疾病中的交叉互动. 生理学报, 2009, 284(44): 30167-30176.

Chinese Journal of Respiratory and Critical Care Medicine

The mechanism of Wnt5a and its receptor in bronchiectasis

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