Exosomal miR-21-5p derived from multiple myeloma cells promote renal epithelial-mesenchymal transition through...

Area of Science:

• Nephrology
• Oncology
• Molecular Biology

Background:

• Multiple myeloma (MM) is associated with poor prognosis in patients with renal insufficiency.
• Renal fibrosis, driven by epithelial-mesenchymal transition (EMT), is a key pathological factor in MM-related kidney disease.
• The precise mechanisms linking MM to renal insufficiency and fibrosis remain unclear.

Purpose of the Study:

• To investigate the role of MM cell-derived exosomes in promoting renal EMT.
• To elucidate the involvement of microRNA-21 (miR-21) in this process.
• To identify the specific molecular pathways targeted by exosomal miR-21.

Main Methods:

• Co-culture of human renal proximal tubular epithelial cells (HK-2) with MM cell-derived exosomes.
• Analysis of EMT markers (E-cadherin, Vimentin) and TGF-β/SMAD7 signaling pathway components.
• Inhibition of miR-21 expression in MM cells and subsequent assessment of exosome effects on HK-2 cells.

Main Results:

• MM cell-derived exosomes induced EMT in HK-2 cells, decreasing E-cadherin and increasing Vimentin.
• Exosomes suppressed SMAD7 expression and increased TGF-β levels, indicating activation of the TGF-β/SMAD7 pathway.
• Inhibiting miR-21 in MM cells reduced miR-21 in exosomes and attenuated the EMT-promoting effect on HK-2 cells.

Conclusions:

• Exosomal miR-21 derived from multiple myeloma cells promotes renal EMT.
• This promotion occurs through the targeting of the TGF-β/SMAD7 signaling pathway.
• These findings highlight exosomal miR-21 as a potential therapeutic target for MM-related kidney disease.