TGF-β/LAMB3 axis drives ROS-dependent renal fibrosis under hypoxic conditions

Area of Science:

• Nephrology
• Molecular Biology
• Pathology

Background:

• Hypoxia is a known cause of renal fibrosis, but its mechanisms are not fully understood.
• Reactive oxygen species (ROS) are implicated in kidney disease progression.
• The role of LAMB3 in hypoxic renal fibrosis requires further elucidation.

Purpose of the Study:

• To investigate the role of ROS in hypoxia-induced renal fibrosis.
• To explore the TGF-β/LAMB3 signaling axis in the context of kidney fibrosis.
• To evaluate the therapeutic potential of ROS scavenging and LAMB3 inhibition.

Main Methods:

• Utilized integrated ATAC-seq and RNA-seq analysis.
• Employed a mouse model of hypoxic renal fibrosis.
• Investigated the effects of N-acetylcysteine (NAC) and kidney-targeted LAMB3 knockdown.

Main Results:

• Hypoxia-induced ROS in renal tubular epithelial cells promote partial epithelial-mesenchymal transition (pEMT) and TGF-β secretion.
• TGF-β upregulates LAMB3 in fibroblasts via enhanced chromatin accessibility.
• Knockdown of LAMB3 ameliorates hypoxia-induced renal fibrosis, and NAC treatment disrupts the TGF-β/LAMB3 axis.

Conclusions:

• The TGF-β/LAMB3 axis drives ROS-dependent renal fibrosis under hypoxic conditions.
• LAMB3 and ROS are identified as potential therapeutic targets for fibrotic kidney diseases.
• Targeting ROS and LAMB3 offers a promising therapeutic strategy for kidney fibrosis.