More than three-quarters of cases of chronic kidney disease are caused by glomerular diseases with glomerulosclerosis, including diabetic kidney disease, hypertensive nephropathy and glomerulonephritis. Studies in 2022 provided insights into the molecular mechanisms that maintain dynamic glomerular structures and the responses of specific glomerular cell types during glomerular disease.
Key advances
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Drosophila nephrocytes rely on rapid endocytosis and recycling of the fly orthologue of nephrin to maintain the structural integrity of the slit diaphragm2.
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The slit diaphragm might act as a molecular sensor that regulates filtration barrier plasticity3.
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Adaptive remodelling of the ventral actin cytoskeleton and integrin adhesion complexes to maintain podocyte attachment to the glomerular basement membrane is dependent on the actin-binding protein α-parvin4.
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The histone deacetylase inhibitor panobinostat promotes differentiation of progenitor parietal epithelial cells to podocytes and has renoprotective effects in experimental crescentic glomerulonephritis5.
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In a mouse model of early IgA nephropathy, changes in glomerular endothelial cells that promote the recruitment and infiltration of immune cells precede pathogenic transcriptional activation in mesangial cells and podocytes6.
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References
Ebefors, K., Lassén, E., Anandakrishnan, N., Azeloglu, E. U. & Daehn, I. S. Modeling the glomerular filtration barrier and intercellular crosstalk. Front. Physiol. 12, 689083 (2021).
Lang, K. et al. Selective endocytosis controls slit diaphragm maintenance and dynamics in Drosophila nephrocytes. eLife 11, e79037 (2022).
Kocylowski, M. K. et al. A slit-diaphragm-associated protein network for dynamic control of renal filtration. Nat. Commun. 13, 6446 (2022).
Rogg, M. et al. α-Parvin defines a specific integrin adhesome to maintain the glomerular filtration barrier. J. Am. Soc. Nephrol. 33, 786–808 (2022).
Melica, M. E. et al. Differentiation of crescent-forming kidney progenitor cells into podocytes attenuates severe glomerulonephritis in mice. Sci. Transl. Med. 14, eabg3277 (2022).
Zambrano, S. et al. Molecular insights into the early stage of glomerular injury in IgA nephropathy using single-cell RNA sequencing. Kidney Int. 101, 752–765 (2022).
Acknowledgements
The authors’ work was supported by US National Institutes of Health grant R01DK097253 and US Department of Defense CDMRP grant E01 W81XWH2010836 to I.S.D.
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I.S.D. has a consultancy agreement with RUMI.
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Lassén, E., Daehn, I.S. Insights into glomerular function and disease pathogenesis. Nat Rev Nephrol 19, 85–86 (2023). https://doi.org/10.1038/s41581-022-00667-9
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DOI: https://doi.org/10.1038/s41581-022-00667-9