Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation

Cheng, Demin; Wang, Yue; Xiong, Haojie; Sun, Wenqing; Xi, Sichuan; Zhou, Shuai; Liu, Yi; Ni, Chunhui

doi:10.1172/jci.insight.162831

Cited by 7 publications

(2 citation statements)

References 39 publications

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“…A recent study showed that TGF-β1-mediated upregulation of UHRF1 repressed beclin 1 via methylated induction of its promoter, which nally resulted in broblast activation and lung brosis both in vitro and in vivo. Moreover, knockdown of UHRF1 signi cantly arrested broblast proliferation and reactivated beclin 1 in lung broblasts [25] . GJA1, also known as Cx43, is one of these connexins.…”

Section: Discussionmentioning

confidence: 97%

The pathogenesis of Acute Exogenous Lipid Pneumonia based on proteomics

Weng,

Wang,

et al. 2023

Preprint

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Introduction Acute exogenous lipoid pneumonia (AELP) is a rare disease. At present, the specific pathogenesis of AELP is unclear, and there is no safe and effective specific drug. The purpose of this study is to explore the biological processes, signal pathways and key proteins involved in AELP through proteomics, bioinformatics and polymerase chain reaction, so as to deepen the study of the pathogenesis of AELP. Methods The experimental rats were randomly divided into 2 groups: experiment group (inhaled 0.5 ml/kg of sewing machine oil) and control group (inhaled 0.5 ml/kg of normal saline). Collect the proteins in the upper lobe of the right lung of mice for proteomic sequencing to obtain the expression data, use the differential analysis software MaxQuant to screen the differentially expressed proteins (DEPs), and use the bioinformatics analysis method to carry out gene ontology function (GO), Kyoto Encyclopedia of genes and genomes (KEGG) analysis and protein-protein interaction (PPI) network construction for DEGs, Eleven key proteins (PADI4, IGF2, SMPDL3B, UHRF1, ANXA8, DEFB4, F3, MK167, SLC39A4, LIMD1 and GJA1) were detected by Reverse-transcription polymerase chain reaction (RT-PCR) for validation. Results A total of 1253 DEPs were obtained after comparing the data of the experimental group and the control group with the proteome, including 843 up-regulated proteins and 410 down-regulated proteins. Through the functional analysis of GO and KEGG, it is found that these DEPs mainly participate in the regulation process of integrin binding, proteoglycan binding, chemokine receptor binding, receiver regulator binding, and cytokine activity, and are significantly enriched in proteoglycan binding and other signal pathways. PPI network construction was carried out for DEPs to screen out proteins with high correlation, such as ACTN3, CX3CR1, CCR3, AGT, MYLPF. 11 proteins were verified by RT-PCR，compared with the control group, 9 proteins (PADI4, IGF2, SMPDL3B, UHRF1, ANXA8, MK167, SLC39A4, LIMD1 and GJA1) were significantly up-regulated in the experimental group. Conclusion Our findings identified that PADI4, IGF2, UHRF1, DEFB4 and GJA1 proteins may be potential diagnostic biomarker of AELP.

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Section: Discussionmentioning

confidence: 97%

The pathogenesis of Acute Exogenous Lipid Pneumonia based on proteomics

Weng,

Wang,

et al. 2023

Preprint

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“…The activation of fibroblasts driven by diverse stimulating factors represents a central event in the development of silica-induced pulmonary fibrosis. Consequently, targeting and impeding this process could hinder the progression of silica-induced pulmonary fibrosis [7,8].…”

Section: Introductionmentioning

confidence: 99%

MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis

Jiang,

Zhao,

Jia

et al. 2023

IJMS

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Silicosis is a fatal occupational respiratory disease caused by the prolonged inhalation of respirable silica. The core event of silicosis is the heightened activity of fibroblasts, which excessively synthesize extracellular matrix (ECM) proteins. Our previous studies have highlighted that human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) hold promise in mitigating silicosis and the significant role played by microRNAs (miRNAs) in this process. Delving deeper into this mechanism, we found that miR-148a-3p was the most abundant miRNA of the differential miRNAs in hucMSC-EVs, with the gene heat shock protein 90 beta family member 1 (Hsp90b1) as a potential target. Notably, miR-148a-3p’s expression was downregulated during the progression of silica-induced pulmonary fibrosis both in vitro and in vivo, but was restored after hucMSC-EVs treatment (p < 0.05). Introducing miR-148a-3p mimics effectively hindered the collagen synthesis and secretion of fibroblasts induced by transforming growth factor-β1 (TGF-β1) (p < 0.05). Confirming our hypothesis, Hsp90b1 was indeed targeted by miR-148a-3p, with significantly reduced collagen activity in TGF-β1-treated fibroblasts upon Hsp90b1 inhibition (p < 0.05). Collectively, our findings provide compelling evidence that links miR-148a-3p present in hucMSC-EVs with the amelioration of silicosis, suggesting its therapeutic potential by specifically targeting Hsp90b1, thereby inhibiting fibroblast collagen activities. This study sheds light on the role of miR-148a-3p in hucMSC-EVs, opening avenues for innovative therapeutic interventions targeting molecular pathways in pulmonary fibrosis.

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