Correlation research on miR-125a-5p in bronchoalveolar lavage fluid with disease severity and pulmonary function in patients with silicosis

doi:10.3877/cma.j.issn.1674-6902.2025.04.012

Abstract

Abstract:

Objective

To analyze the relationship between the level of miR-125a-5p in bronchoalveolar lavage fluid (BALF) and the severity of disease and lung function in silicosis patients.

Methods

A total of 109 patients with silicosis who underwent bronchoalveolar lavage and were admitted to our hospital from March 2019 to April 2024 were selected as the subjects. They were grouped according to the severity of the disease. 53 cases in stage 0 were the control group, and 56 cases in stages Ⅰ to Ⅲ were the observation group. The level of miR-125a-5p in BALF was analyzed by real-time fluorescence quantitative polymerase chain amplification, and the lung functions and BALF cytokines of the two groups were compared.

Results

The level of BALF miR-125a-5p in the observation group was significantly higher than that in the control group [3.26 (2.25, 3.82) vs. 1.06 (0.62, 1.32), Z=-8.052, P<0.001]. Multivariate Logistics regression analysis showed that combined smoking history and BALF miR-125a-5p level were independent risk factors for silicosis in workers, and the variation of BALF miR-125a-5p level between the observation group and the silicosis group was clustered (effect estimate=22.670, P=0.029), and the fixed effect of smoking history [HR: 4.395, 95%CI: 1.671~11.559, P=0.003] on BALF miR-125a-5p level[HR: 47.848, 95%CI: 4.396~520.783, P<0.001] was statistically significant (F=158.993, P<0.001). The area under the working characteristic curve of BALF miR-125a-5p level for the diagnosis of silicosis was 0.947 (95%CI: 0.887~0.981), and the sensitivity and specificity of BALF miR-125a-5p level for the diagnosis of silicosis were 89.29% and 90.57%, respectively. In the silicosis group, 31 cases (55.36%) were stage Ⅰ, 16 cases (28.57%) were stage Ⅱ, and 9 cases (16.07%) were stage Ⅲ. The levels of BALF miR-125a-5p in patients with stage Ⅰ2.36(1.84, 3.26), stage Ⅱ3.50 (3.26, 4.10), and stage Ⅲ4.25 (3.50, 4.42) silicosis were significantly higher than those in the control group 1.06 (0.62, 1.32) (H=70.774, P<0.001), and the levels of BALF miR-125a-5p in stage Ⅰ to Ⅲ silicosis patients increased stage by stage. The median value of BALF miR-125a-5p in patients with silicosis was 3.26. In patients with BALF miR-125a-5p≥3.26, VC[(69.71±5.33)% vs. (75.50±2.44)%, t=5.161, P<0.001], FEV₁[ (78.24±12.20)% vs. (85.39±13.10)%, t=2.115, P=0.039], FVC[(71.39±11.25)% vs. (80.64±12.39)%, t=2.928, P=0.005] and DL_CO[ (61.22±11.12)% vs. (72.19±14.82)%, t=3.147, P=0.003] were lower than those in patients with BALF miR-125a-5p<3.26. Patients with BALF miR-125a-5p≥3.26 had a high probability of developing restrictive ventilator dysfunction [26(89.66%) vs. 11(40.74%), P<0.001]. Spearman rank correlation analysis showed that the expression level of BALF miR-125a-5p was positively correlated with the levels of interleukin (IL) -5, IL-6, IL-17A, interferon-induced protein 10(IP-10) and tumor necrosis factor α(TNF-α) in silicosis patients (r_s=0.299~0.671, P<0.05).

Conclusion

The high level of BALF miR-125a-5p is significantly correlated with the increase of silicosis severity and the decrease of lung function.

Key words: Silicosis, Bronchoalveolar lavage fluid, miR-125a-5p, Silicosis, Disease severity, Lung function

Yu Luo, Zhangan Yuan, Yangming Yu, Dingjun Wang, Zhonglin Xiong, Ningfang Jiang. Correlation research on miR-125a-5p in bronchoalveolar lavage fluid with disease severity and pulmonary function in patients with silicosis[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(04): 564-569.

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References 30

1	Austin EK, James C, Tessier J. Early detection methods for silicosis in australia and internationally: A review of the literature[J]. Int J Environ Res Public Health, 2021, 18(15): 8123.
2	Li T, Yang X, Xu H, et al. Early identification, accurate diagnosis, and treatment of silicosis[J]. Can Respir J, 2022, 2022: 3769134.
3	Handra CM, Gurzu IL, Chirila M, et al. Silicosis: New challenges from an old inflammatory and fibrotic disease[J]. Front Biosci (Landmark Ed), 2023, 28(5): 96.
4	李丹，张乙，张丽娟，等. N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸对二氧化硅致大鼠矽肺纤维化中巨噬细胞活化的调节作用[J]. 环境与健康杂志，2021, 38(1): 20-25.
5	何汶芮，杨帆，侯润苏，等. 基于代谢组学探讨金水尘肺方改善二氧化硅诱导大鼠矽肺肺纤维化的作用机制研究[J]. 中国中西医结合急救杂志，2023, 30(6): 657-663.
6	田王斌，金发光，顾兴，等. 巨噬细胞移动抑制因子在慢性阻塞性肺疾病发病中的作用及机制研究进展[J/CD]. 中华肺部疾病杂志(电子版), 2019, 12(1): 112-114.
7	程鸿明，何海兰，王袁，等. 基于生物信息学分析筛选矽肺患者肺泡巨噬细胞中线粒体靶向标志物[J]. 安徽医科大学学报，2024, 59(10): 1828-1834，1841.
8	Li R, Kang H, Chen S. From basic research to clinical practice: considerations for treatment drugs for silicosis[J]. Int J Mol Sci, 2023, 24(9): 8333.
9	You Y, Wu X, Yuan H, et al. Crystalline silica-induced recruitment and immuno-imbalance of CD4(＋) tissue resident memory T cells promote silicosis progression[J]. Commun Biol, 2024, 7(1): 971.
10	Ding M, Pei Y, Zhang C, et al. Exosomal miR-125a-5p regulates T lymphocyte subsets to promote silica-induced pulmonary fibrosis by targeting TRAF6[J]. Ecotoxicol Environ Saf, 2023, 249: 114401.
11	Wang R, Zhu Z, Peng S, et al. Exosome microRNA-125a-5p derived from epithelium promotes M1 macrophage polarization by targeting IL1RN in chronic obstructive pulmonary disease[J]. Int Immunopharmacol, 2024, 137: 112466.
12	Li M, Li Y, Liu Q, et al. Exosomal miR-552-3p isolated from BALF of patients with silicosis induces fibroblast activation[J]. Toxicol Lett, 2024, 401: 55-70.
13	Castro MCS, Nani ASF, Salum KCR, et al. Genetic polymorphisms and their effects on the severity of silicosis in workers exposed to silica in Brazil[J]. J Bras Pneumol, 2022, 48(5): e20220167.
14	Li S, Zhao J, Han G, et al. Silicon dioxide-induced endoplasmic reticulum stress of alveolar macrophages and its role on the formation of silicosis fibrosis: a review article[J]. Toxicol Res (Camb), 2023, 12(6): 1024-1033.
15	Adamcakova J, Mokra D. New insights into pathomechanisms and treatment possibilities for lung silicosis[J]. Int J Mol Sci, 2021, 22(8): 4162.
16	Song MY, Wang JX, Sun YL, et al. Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages[J]. Acta Pharmacol Sin, 2022, 43(5): 1274-1284.
17	Zhou X, Zhang C, Yang S, et al. Macrophage-derived MMP12 promotes fibrosis through sustained damage to endothelial cells[J]. J Hazard Mater, 2024, 461: 132733.
18	Hua JT, Cool CD, Green FHY. Pathology and mineralogy of the pneumoconioses[J]. Semin Respir Crit Care Med, 2023, 44(3): 327-339.
19	Howlett P, Gan J, Lesosky M, et al. Relationship between cumulative silica exposure and silicosis: a systematic review and dose-response meta-analysis[J]. Thorax, 2024, 79(10): 934-942.
20	Liu TT, Sun HF, Han YX, et al. The role of inflammation in silicosis[J]. Front Pharmacol, 2024, 15: 1362509.
21	Malainou C, Abdin SM, Lachmann N, et al. Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting[J]. J Clin Invest, 2023, 133(19): e170501.
22	Pervizaj-Oruqaj L, Ferrero MR, Matt U, et al. The guardians of pulmonary harmony: alveolar macrophages orchestrating the symphony of lung inflammation and tissue homeostasis[J]. Eur Respir Rev, 2024, 33(172): 230263.
23	Wohnhaas CT, Baßler K, Watson CK, et al. Monocyte-derived alveolar macrophages are key drivers of smoke-induced lung inflammation and tissue remodeling[J]. Front Immunol, 2024, 15: 1325090.
24	Li X, Mara AB, Musial SC, et al. Coordinated chemokine expression defines macrophage subsets across tissues[J]. Nat Immunol, 2024, 25(6): 1110-1122.
25	Yang G, Yang Y, Liu Y, et al. Regulation of alveolar macrophage death in pulmonary fibrosis: a review[J]. Apoptosis, 2023, 28(11-12): 1505-1519.
26	Huang L, Zhang Y, Yang J, et al. Anti-fibrotic effects and the mechanism of action of miR-29c in silicosis[J]. Mol Med Rep, 2021, 23(4): 292.
27	Niu Z, Wang L, Qin X, et al. Macrophage derived miR-7219-3p-containing exosomes mediate fibroblast trans-differentiation by targeting SPRY1 in silicosis[J]. Toxicology, 2022, 479: 153310.
28	Chang Y, Han JA, Kang SM, et al. Clinical impact of serum exosomal microRNA in liver fibrosis[J]. PLoS One, 2021, 16(9): e0255672.
29	Zhu K, Xu A, Xia W, et al. Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis[J]. Int J Med Sci, 2021, 18(15): 3412-3424.
30	Ding M, Zhang C, Wang W, et al. Silica-exposed macrophages-secreted exosomal miR125a-5p induces Th1/Th2 and Treg/Th17 cell imbalance and promotes fibroblast transdifferentiation[J]. Ecotoxicol Environ Saf, 2023, 267: 115647.

临床资料	对照组(n＝53)	观察组(n＝56)	Z/t/χ²	P值
体质量指数[kg/m²，(±s)]	22.71±5.53	21.68±2.40	1.273	0.206
吸烟史[n(%)]	22(41.51)	38(67.86)	7.639	0.006
饮酒史[n(%)]	26(49.06)	30(53.57)	0.222	0.637
暴露年限[年，(±s)]	17.85±5.29	18.62±6.71	0.663	0.509
BALF参数
总细胞计数[×10⁷/ml，(±s)]	10.46±3.39	10.24±3.27	0.345	0.731
中性粒细胞百分比[%，(±s)]	50.66±14.81	59.16±17.82	2.700	0.008
淋巴细胞百分比[%，(±s)]	36.17±12.84	42.88±12.65	2.748	0.007
影像学结果[n(%)]
磨玻璃影	5(9.43)	19(33.93)	9.515	0.002
实变影	2(3.77)	16(28.57)	12.151	0.000
点片状影	9(16.98)	20(35.71)	4.894	0.027
纤维索条影	4(7.55)	24(42.86)	17.782	0.000
胸膜增厚	4(7.55)	15(26.79)	7.002	0.008
肺功能指标[%，(±s)]
VC	87.71±11.17	72.34±5.13	9.313	0.000
FEV₁	95.18±10.80	81.69±13.03	5.867	0.000
FVC	89.80±9.40	75.78±12.63	6.545	0.000
FEV₁/FVC	83.59±7.49	79.64±8.10	2.639	0.010
DL_CO	74.03±17.32	65.72±13.72	2.784	0.006
RV/TLC[M₅₀(P₂₅，P₇₅)]	22.00(17.00，27.25)	23.00(18.50，28.00)	－0.439	0.661
BALF miR-125a-5p[M₅₀(P₂₅，P₇₅)]	1.06(0.62，1.32)	3.26(2.25，3.82)	－8.052	0.000

临床资料	对照组(n＝53)	观察组(n＝56)	Z/t/χ²	P值
体质量指数[kg/m²，(±s)]	22.71±5.53	21.68±2.40	1.273	0.206
吸烟史[n(%)]	22(41.51)	38(67.86)	7.639	0.006
饮酒史[n(%)]	26(49.06)	30(53.57)	0.222	0.637
暴露年限[年，(±s)]	17.85±5.29	18.62±6.71	0.663	0.509
BALF参数
总细胞计数[×10⁷/ml，(±s)]	10.46±3.39	10.24±3.27	0.345	0.731
中性粒细胞百分比[%，(±s)]	50.66±14.81	59.16±17.82	2.700	0.008
淋巴细胞百分比[%，(±s)]	36.17±12.84	42.88±12.65	2.748	0.007
影像学结果[n(%)]
磨玻璃影	5(9.43)	19(33.93)	9.515	0.002
实变影	2(3.77)	16(28.57)	12.151	0.000
点片状影	9(16.98)	20(35.71)	4.894	0.027
纤维索条影	4(7.55)	24(42.86)	17.782	0.000
胸膜增厚	4(7.55)	15(26.79)	7.002	0.008
肺功能指标[%，(±s)]
VC	87.71±11.17	72.34±5.13	9.313	0.000
FEV₁	95.18±10.80	81.69±13.03	5.867	0.000
FVC	89.80±9.40	75.78±12.63	6.545	0.000
FEV₁/FVC	83.59±7.49	79.64±8.10	2.639	0.010
DL_CO	74.03±17.32	65.72±13.72	2.784	0.006
RV/TLC[M₅₀(P₂₅，P₇₅)]	22.00(17.00，27.25)	23.00(18.50，28.00)	－0.439	0.661
BALF miR-125a-5p[M₅₀(P₂₅，P₇₅)]	1.06(0.62，1.32)	3.26(2.25，3.82)	－8.052	0.000

影响因素	β	SE	Walds值	HR(95%CI)	P值
吸烟史(0＝否，1＝是)	1.480	0.493	9.003	4.395(1.671~11.559)	0.003
中性粒细胞百分比	0.064	0.053	1.498	1.067(0.962~1.182)	0.221
淋巴细胞百分比	0.077	0.132	0.336	1.080(0.833~1.399)	0.562
VC	0.042	0.053	0.641	1.043(0.941~1.156)	0.423
FEV₁	－0.601	0.329	3.329	0.548(0.287~1.046)	0.068
FVC	0.466	0.292	2.538	1.593(0.898~2.826)	0.111
FEV₁/FVC	0.691	0.354	3.822	1.996(0.998~3.991)	0.051
DL_CO	0.001	0.032	0.000	1.001(0.939~1.066)	0.986
BALF miR-125a-5p	3.868	1.218	10.085	47.848(4.396~520.783)	0.001

影响因素	β	SE	Walds值	HR(95%CI)	P值
吸烟史(0＝否，1＝是)	1.480	0.493	9.003	4.395(1.671~11.559)	0.003
中性粒细胞百分比	0.064	0.053	1.498	1.067(0.962~1.182)	0.221
淋巴细胞百分比	0.077	0.132	0.336	1.080(0.833~1.399)	0.562
VC	0.042	0.053	0.641	1.043(0.941~1.156)	0.423
FEV₁	－0.601	0.329	3.329	0.548(0.287~1.046)	0.068
FVC	0.466	0.292	2.538	1.593(0.898~2.826)	0.111
FEV₁/FVC	0.691	0.354	3.822	1.996(0.998~3.991)	0.051
DL_CO	0.001	0.032	0.000	1.001(0.939~1.066)	0.986
BALF miR-125a-5p	3.868	1.218	10.085	47.848(4.396~520.783)	0.001

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