Fine particulate matter (PM_2.5) induces microRNA-192-5p causing glomerular damage

Area of Science:

• Nephrology
• Environmental Health
• Molecular Biology

Background:

• Epidemiological studies suggest a link between air pollution and membranous glomerulonephritis (MGN).
• The precise causal relationship and underlying pathomechanisms, including the role of anti-phospholipase A2 receptor (PLA2R1) antibodies and microRNA-192-5p, remain unclear.
• The trigger for these molecular changes in MGN pathogenesis is unknown.

Purpose of the Study:

• To investigate the potential role of fine particulate matter (PM2.5) in the pathogenesis of membranous glomerulonephritis (MGN).
• To characterize PM2.5 and assess its effects on glomerular function and ultrastructure in vitro and in vivo.

Main Methods:

• Characterization of PM2.5 using various spectroscopic and microscopic techniques.
• Exposure of cultured human podocytes, zebrafish, and mice to PM2.5.
• Assessment of glomerular markers, gene expression (microRNA-192-5p, NPNT, PLA2R1), kidney function (proteinuria, albuminuria), and glomerular ultrastructure.
• Analysis of inflammatory response and oxidative stress via BulkRNA seq and qPCR in zebrafish.

Main Results:

• PM2.5 exposure reduced podocyte-specific markers and upregulated microRNA-192-5p.
• Downregulation of nephronectin (NPNT) and upregulation of PLA2R1 were observed following PM2.5 exposure.
• Zebrafish larvae exposed to PM2.5 exhibited edema, proteinuria, glomerular damage, and increased inflammatory and oxidative stress markers.
• Mice exposed to ambient PM2.5 developed glomerular damage, albuminuria, and pulmonary microRNA-192-5p upregulation.

Conclusions:

• PM2.5 may contribute to the development of MGN through inflammatory pathways.
• PM2.5 can induce microRNA-192-5p, affecting gene expression critical for glomerular cell function.
• These findings suggest a potential causal link between air pollution and MGN pathogenesis.