TY - JOUR
T1 - Extracellular vesicle miR-93-5p cargo regulates glomerular endothelial cell damage in Alport syndrome
AU - Dedhia, Charmi
AU - Villani, Valentina
AU - Hou, Xiaogang
AU - Neviani, Paolo
AU - Clair, Geremy
AU - Kasravi, Mohammadreza
AU - Grange, Cristina
AU - Cravedi, Paolo
AU - Aguiari, Paola
AU - Alcala, Velia
AU - Orlando, Giuseppe
AU - Song, Xue Ying
AU - Zuckerman, Jonathan E.
AU - De Filippo, Roger E.
AU - Sacco, Stefano Da
AU - Sedrakyan, Sargis
AU - Bussolati, Benedetta
AU - Perin, Laura
N1 - Publisher Copyright:
© 2026, Dedhia et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2026/1
Y1 - 2026/1
N2 - Modulation of miRNA expression in glomerular cells is associated with renal disease. Here, we investigated the role of miR-93-5p in mitigating glomerular damage in Alport syndrome and whether the disease-modifying activity of extracellular vesicles from human amniotic fluid stem cells (hAFSC-EVs) is mediated by their miR-93-5p cargo. We identified downregulation of miR 93-5p specifically in glomerular endothelial cells in Alport syndrome along disease progression. Silencing of miR-93-5p in hAFSC-EVs changed the transcriptomic and proteomic profile, regulating EV disease-modifying activity. Compared with naive hAFSC-EVs, silenced hAFSC-EVs did not rescue glomerular endothelial function in vitro and did not restore kidney function in vivo. We established that hAFSC-EVs regulate VEGFR1 and VEGFR2 signaling by miR-93-5p cargo transfer, highlighting that miR-93-5p can restore glomerular endothelial cell biology. Spatial transcriptomics analysis of hAFSC-EV–injected kidneys showed that these EVs can reverse pathways altered during disease progression by stimulating proregenerative processes, specifically in the glomerulus, by regulating miR-93-5p targets. Alteration of glomerular endothelial cell transcriptomics and miR-93-5p targets was also confirmed in biopsies of patients with Alport syndrome using spatial molecular imaging. We demonstrated the critical role of miR-93-5p in glomerular endothelial cells and the capability of hAFSC-EVs to regulate miR-93-5p and its targets in Alport syndrome.
AB - Modulation of miRNA expression in glomerular cells is associated with renal disease. Here, we investigated the role of miR-93-5p in mitigating glomerular damage in Alport syndrome and whether the disease-modifying activity of extracellular vesicles from human amniotic fluid stem cells (hAFSC-EVs) is mediated by their miR-93-5p cargo. We identified downregulation of miR 93-5p specifically in glomerular endothelial cells in Alport syndrome along disease progression. Silencing of miR-93-5p in hAFSC-EVs changed the transcriptomic and proteomic profile, regulating EV disease-modifying activity. Compared with naive hAFSC-EVs, silenced hAFSC-EVs did not rescue glomerular endothelial function in vitro and did not restore kidney function in vivo. We established that hAFSC-EVs regulate VEGFR1 and VEGFR2 signaling by miR-93-5p cargo transfer, highlighting that miR-93-5p can restore glomerular endothelial cell biology. Spatial transcriptomics analysis of hAFSC-EV–injected kidneys showed that these EVs can reverse pathways altered during disease progression by stimulating proregenerative processes, specifically in the glomerulus, by regulating miR-93-5p targets. Alteration of glomerular endothelial cell transcriptomics and miR-93-5p targets was also confirmed in biopsies of patients with Alport syndrome using spatial molecular imaging. We demonstrated the critical role of miR-93-5p in glomerular endothelial cells and the capability of hAFSC-EVs to regulate miR-93-5p and its targets in Alport syndrome.
UR - https://www.scopus.com/pages/publications/105034085293
U2 - 10.1172/jci.insight.197643
DO - 10.1172/jci.insight.197643
M3 - Article
C2 - 41869725
AN - SCOPUS:105034085293
SN - 2379-3708
VL - 11
SP - 1
EP - 18
JO - JCI insight
JF - JCI insight
IS - 6
M1 - e197643
ER -