Kidney Week 2025 Annual Meeting-Post-Transcriptional and Post-Translational Processing in Glomerular Diseases

Video Transcription

Video Summary

The session focused on RNA and post‑transcriptional regulation in kidney disease, especially diabetic kidney disease (DKD) and glomerular disorders.<br /><br />One speaker reviewed how non‑coding RNAs regulate DKD. MicroRNAs (small non‑coding RNAs) typically suppress target mRNAs. Their group found miR‑93 is reduced in diabetic conditions; restoring miR‑93 (genetically or with mimics) reduced albuminuria and improved kidney histology in diabetic mice. Mechanistically, miR‑93 targets VEGF and MSK2, linking miR‑93 to epigenetic/chromatin remodeling via histone H3 phosphorylation. The talk then shifted to long non‑coding RNAs (lncRNAs), highlighting TUG1, which is also decreased in DKD and correlates with worse kidney function in patient datasets. Podocyte‑specific TUG1 overexpression improved albuminuria and pathology. TUG1 appears to act as a scaffold that promotes PGC‑1α transcription, supporting mitochondrial biogenesis/function; knocking down PGC‑1α removed TUG1’s benefit. They also reported TUG1 encodes a mitochondria‑localized micropeptide (detected by mass spectrometry) whose function is under study.<br /><br />A second speaker presented alternative splicing and alternative polyadenylation as underexplored drivers of podocyte injury in minimal change disease and FSGS models. They identified disease‑associated splicing changes (notably in ITM2B and TJP1/ZO‑1) that alter isoform ratios and cytoskeletal/slit diaphragm organization. Splice‑switching oligonucleotides could experimentally shift TJP1 exon inclusion and changed podocyte markers and actin architecture, suggesting therapeutic potential. They also mapped RNA‑binding protein regulators and GWAS SNPs that may influence these RNA processing events.<br /><br />Another speaker discussed IgA glycosylation in IgA nephropathy, finding strong disease associations not only with hinge O‑glycans (sialylation/galactose deficiency) but also with IgA N‑glycans, and suggested mucosal (gut) origins and gut‑targeted therapies.<br /><br />Finally, work on DKD showed that podocyte SHP1 promotes disease progression; podocyte SHP1 deletion prevented or halted worsening albuminuria and pathology. Proteomics implicated SUMOylation, with diabetes reducing SUMO2‑linked modification of podocin; restoring this pathway may stabilize podocyte structure.

Asset Subtitle

Moderator(s): John He, Sandra Merscher

Presentation(s):

miRNAs and lncRNAs in DKD - Farhad Danesh
mRNA Alternative Splicing and Polyadenylation Regulates the Slit Diaphragm in Glomerular Diseases - Shipra Agrawal
Association of Glycosylation of Serum IgA with IgAN and Glomerular Function - Mario Falchi
SUMOylation of Podocin Reverses the Progression of DKD - Pedro Geraldes

Support for all sessions in the Glomerular Diseases Learning Pathway is provided by an educational grant from Vera Therapeutics, Inc.

Meta Tag

Date 11/6/2025

Pathway 1 Glomerular Diseases

Pathway 2 Diabetic Kidney Disease

Session ID 507112

Keywords

RNA regulation

post-transcriptional regulation

diabetic kidney disease

glomerular disorders

microRNA miR-93

VEGF targeting

MSK2

histone H3 phosphorylation

long non-coding RNA TUG1

PGC-1α transcription

mitochondrial biogenesis

alternative splicing

TJP1/ZO-1 isoforms

splice-switching oligonucleotides

IgA nephropathy glycosylation