Objective: To investigate the impact of Mongolian medicine saorilao-4 (SRL-4) on miRNA and core genes involved in the gene regulatory network of lung tissue in rats with pulmonary fibrosis (PF). Methods: Rats were randomly divided into four groups: blank control group (CON), model group (MOD), positive drug control group, and SRL-4 group. Except for the CON group, rats in the other groups were administered with bleomycin via intratracheal injection to establish a pulmonary fibrosis model. The total RNA was extracted from rat lung tissue for transcriptome sequencing. The differentially expressed miRNA (DEM) in each group was screened by the difference analysis software edge R. The differentially expressed gene (DEG) of DEM was predicted by miRanda. The GO and KEGG were used to analyze the biological function enrichment of DEG. Cytoscape was used to construct the target gene regulatory network and screen the core genes. Results: Compared with CON, MOD selected 16 DEMs. Compared with MOD, SRL-4 screened 10 DEMs and regulated 63 052 target genes. GO analysis showed that the DEGs of SRL-4 and MOD were enriched in 52 GO entries. KEGG analysis showed that DEG was enriched in 182 signaling pathways, among which the number of genes related to purine metabolic pathway was the highest. By constructing a gene regulatory network, six core genes were screened, namely Spata25, Sultan1a1, Mpv17i, Cryba4, Jakmip3 and Fkbp5. Conclusion: By constructing a miRNA-Target regulatory network between SRL-4 and MOD, we identified six hub genes that are considered key molecules in the gene regulatory network for the treatment of PF. The improvement effect of SRL-4 on PF may be related to miR-433-3p, novel_202, miR-150-3p, and these 6 core genes. The purine metabolism-related signaling pathway may be a critical target and essential pathway for the treatment of PF.
FU Xinyue
,
SONG Xinni
,
LIU Jiali
,
LIU Yujian
,
SHI Songli
,
NIU Shufang
,
CHANG Hong
,
WANG Peng
,
QI Jun
,
BAI Wanfu
. MicroRNAs comparison and regulatory network analysis of Mongolian medicine Saurilao-4 in the treatment of pulmonary fibrosis in rats[J]. Journal of Baotou Medical College, 2025
, 41(5)
: 6
-14
.
DOI: 10.16833/j.cnki.jbmc.2025.05.002
[1] Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic pulmonary fibrosis. an official ATS/ERS/JRS/ALAT clinical practice guideline[J]. Am J Respir Crit Care Med, 2018, 198(5): e44-e68.
[2] Selman M, Pardo A. Revealing thepathogenic and aging-related mechanisms of the enigmatic idiopathic pulmonary fibrosis. An integral model[J]. Am J Respir Crit Care Med, 2014, 189: 1161-1172.
[3] Fingerlin TE, Murphy E, Zhang W, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis[J]. Nat Genet, 2013, 45: 613-620.
[4] Yang S, Xie N, Cui H, et al. MiR-31 is a negative regulator of fibrogenesis and pulmonary fibrosis[J]. FASEB J, 2012, 26(9): 3790-3799.
[5] Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs[J]. Genome Res, 2009, 19(1): 92-105.
[6] 恒泰, 莲花, 阿木古楞. 简述蒙成药扫日劳-4汤[J]. 中国民族医药杂志, 2022, 28(4): 55-56.
[7] 白万富, 刘玉键, 李想, 等. 蒙药扫日劳-4味汤对特发性肺纤维化模型大鼠的改善作用及机制初探[J]. 中国药房, 2021, 32(12): 1435-1441.
[8] 陆松梅, 雷双奕, 李代蓉, 等. miR-433-3p通过靶向下调GALNT1调控肺癌细胞的生物学行为[J]. 中国细胞生物学学报, 2021, 43(11): 2126-2133.
[9] 郭义威, 孙春莉, 王树兴. miR-433在NIH-3T3细胞纤维化和矽尘诱导的小鼠肺纤维化中的作用[J]. 中国病理生理杂志, 2020, 36(8): 1458-1464.
[10] Ghédir H, Braham A, Viville S, et al. Comparison of sperm morphology and nuclear sperm quality in SPATA16- and DPY19L2-mutated globozoospermic patients[J]. Andrologia, 2019, 51(6): e13277.
[11] Dammanahalli JK, Duffel MW. Oxidative modification of rat sulfotransferase 1A1 activity in hepatic tissue slices correlates with effects on the purified enzyme[J]. Drug Metab Dispos, 2012, 40(2): 298-303.
[12] Billingsley G, Santhiya ST, Paterson AD, et al. CRYBA4, a novel human cataract gene, is also involved in microphthalmia[J]. Am J Hum Genet, 2006, 79(4): 702-709.
[13] Zhou J, Jiang G, Xu E, et al. Identification of SRXN1 and KRT6A as key genes in smoking-related non-small-cell lung cancer through bioinformatics and functional analyses[J]. Front Oncol, 2022, 11: 810301.
[14] Sun L, Gang X, Li Z, et al. Advances in understanding the roles of CD244 (SLAMF4) in immune regulation and associated diseases[J]. Front Immunol, 2021, 12: 648182.
[15] 徐玉雪. FKBP51在小鼠肝脏纤维化中的作用以及分子机制的探究[D]. 北京: 北京协和医学院(清华大学医学部)&中国医学科学院, 2016.
[16] 李文超. miRNA调控纳米SiO2诱导肺损伤靶基因作用的初步研究[D]. 江苏: 东南大学, 2015.
[17] Lao C , Li W , Li M ,et al.The biological effect of MiR-541 in rat′s pulmonary fibrosis induced by nanosized SiO2 through targeting TGF-β RIII[J]. Nanomedicine Nanotechnology Biology & Medicine, 2016, 12(2): 563-563.
[18] 蔡萧君, 王钦, 江柏华, 等. 基于粪便代谢组学技术丹贝益肺方对肺纤维化伴抑郁大鼠的作用机制研究[J]. 山西医科大学学报, 2022, 53(2): 175-181.
[19] Jordheim LP, Peters GJ. New insights in research on purine and pyrimidine metabolism[J]. Nucleosides Nucleotides Nucleic Acids, 2022, 41(3): 247-254.
[20] Bueno LCM, Paim LR, Minin EOZ, et al. Increased serum mir-150-3p expression is associated with radiological lung injury improvement in patients with COVID-19[J]. Viruses, 2022, 14(7): 1363.
