Role of LncRNA RP11-20G6.3 and TLR4/NF-κB signaling pathway in airway inflammation and remodeling in COPD
10.19405/j.cnki.issn1000-1492.2022.04.015
- Author:
Xunchun Chen
1
,
2
;
Minglan Li
1
,
2
;
Biyun Pan
1
,
2
;
Yanying Wang
1
,
2
;
Yipeng Ding
3
Author Information
1. Dept of General Medicine，Haikou People'
2. s Hospital，Haikou 570208
3. Dept of Respiratory，Hainan General Hospital，Haikou 570311
- Publication Type:Journal Article
- Keywords:
LncRNA RP11-20G6. 3;
TLR4 / NF-κB signaling pathway;
chronic obstructive pulmonary disease;
airway inflammation;
airway remodeling
- From:
Acta Universitatis Medicinalis Anhui
2022;57(4):586-593
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of LncRNA RP11-20 G6.3 and Toll-like receptor 4(TLR4)/nuclear factor kappa-B(NF-κB) signaling pathway in airway inflammation and remodeling in chronic obstructive pulmonary disease(COPD).
Methods:The wild-type(WT) and TLR4 knock out(KO) C57 BL/6 male mice were used to construct COPD model. The expression of TLR4/NF-κB signaling pathway protein was analyzed by Western blot; the levels of interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in bronchoalveolar lavage fluid( BALF) were detected by enzyme-linked immunosorbent assay( ELISA). The differentially expressed LncRNAs were identified by RNA sequencing and functional enrichment analysis,and the competing endogenous RNAs( ceRNA) networks were predicted using RNAhybrid. Luciferase reporter was used to explore relationships between genes.
Results:In COPD model, compared with WT mice, the lung inflammation of TLR4-/-mice was significantly reduced,the expression of NF-κB related protein,the levels of inflammatory factors( IL-1β,IL-6 and TNF-α) in BALF and Masson trichromatic staining area significantly decreased in TLR4-/-mice. RNA sequencing and functional enrichment analysis confirmed that RP11-20G6. 3 was one of the differentially expressed LncRNA. RP11-20G6. 3 was up-regulated in lung tissue of COPD patients,and its expression was significantly correlated with FEV1( ρ = 0. 549,P = 0. 047). RP11-20G6. 3 plasmid intervention aggravated the inflammation of lung tissue in TLR4-/-COPD mice,and increased the Masson tricolor area around bronchi and the levels of inflammatory factors( IL-1β,IL-6 and TNF-α) in BALF. Luciferase reporter gene analysis showed that RP11-20G6. 3 acted as a ceRNA for miR-34c-5p in COPD,and sponges the latter to upregulate Col1a1.
Conclusion:TLR4/NF-κB relays the damage signals following COPD and activates the downstream RP11-20G6. 3/miR-34c-5p/Col1a1 ceRNA network which triggers airway inflammation and remodeling.
- Full text:2025021814454025840TLR4_NF-κB信号通...阻塞性肺疾病气道炎症和重塑_陈训春.pdf
