Work

Diesel Exhaust‐Induced miR ‐133b‐3p Downregulation and CTGF ‐Linked Hippo Pathway Inactivation Promote ECM Remodeling and Inflammation in Mouse Lungs

Year: 2026

Type: article

Abstract: Exposure to diesel exhaust (DE) significantly contributes to air pollution. DE dysregulates miRNA expression, miRNA-target interactions promoting tissue remodeling and lung inflammation. In the present study, C57BL/6 mice were divided into two groups: one was given DE for 30 min/day, 5 days/week, for 8 weeks whereas the control group was given filtered air. BALF and lungs were collected for cytokine analysis. MiRNA expression was analyzed in lungs using microarrays. qRT-PCR and western blotting validated miRNAs and target genes. Functional impacts of miRNA-target gene interaction were studied using in vitro and in vivo models. DE exposure downregulated miR-133b-3p (> 2-fold, p < 0.05) prompting investigation into downstream effects. In silico analysis identified 371 potential targets of miR-133b-3p, with Hippo signaling as one of the most enriched pathways wherein CTGF, FGF1, and TCF7 genes shared a common predicted binding site for miR-133b-3p. Functional validation using A549 cells showed transfection with miR-133b-3p mimic reduces CTGF expression at both mRNA (p = 0.0054) and protein (p = 0.0001) levels, while inhibition of miR-133b-3p restored CTGF expression, confirming it as a direct target. In vivo, DE exposure increased CTGF mRNA & protein expression whereas decreased P-YAP/YAP ratio was consistent with Hippo pathway dysregulation and co-occurred with miR-133b-3p downregulation. DE exposure also increased pro-inflammatory cytokines (IL-18, IL-1β, GM-CSF) in BALF, indicating increased inflammatory response. Furthermore, DE exposure decreased LOXL1 and LOXL4 mRNA and increased MMP-3, MMP-7, and MMP-12 protein levels therefore altering ECM turnover potential corroborated with STRING analysis. Cumulatively, DE-induced miR-133b-3p downregulation and CTGF alteration are associated with Hippo pathway dysregulation, increased inflammation, and MMP/LOX-driven ECM remodeling in mouse lungs.

Source: Environmental and Molecular Mutagenesis

DOI: 10.1002/em.70088

Authors: Anshu Gautam, Ekta Nagar, Naresh Singh, Neeru Saini, Naveen Arora

Institution: Institute of Genomics and Integrative Biology

Language: English

Topic: MicroRNA in disease regulation

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: Indian Council of Medical Research