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Glomerular endothelial cells (GEnC) form the innermost layer of the glomerular capillary wall which constitutes the glomerular filtration barrier. Normal GEnC possess numerous fenestrations, transcellular pores of 60-80nm in diameter. These fenestrations allow the high hydraulic conductivity of the glomerular filtration barrier, essential for filtration function. The surface of GEnC is, like other endothelial cells, covered by a glycocalyx. This also covers the fenestrations and contributes to the permeability barrier to macromolecules and hence to prevention of passage of albumin and other proteins into the urine.
We are working to understand in detail the contribution of GEnC to the glomerular filtration barrier in terms of the above ultrastructural features and corresponding physiology. We are examining how this normal function is disturbed in disease states and exploring ways of correcting these disturbances therapeutically. We have developed unique conditionally immortalised human GEnC lines to enable detailed studies in vitro.
Specific projects include the role of the glycocalyx and its disturbance by heparanase and by diabetes, regulation and ultrastructure of fenestrations, effects of soluble mediators (VEGF and angiopoietins) on GEnC barrier properties, mechanisms of the anti-proteinuric effect of interferon beta and interactions with podocytes. The later involves development of in vitro models of the glomerular filtration barrier incorporating coculture and flowing medium to induce shear stress.
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- 6 Finished
Aldosterone-enduced endothelial glycocalyx dysfunction, a potential theraputic target in proteinuria? - M Butler fellowship
1/08/15 → 31/07/18
Tuffin, J., Chesor, M., Kuzmuk, V., Johnson, T., Satchell, S. C., Welsh, G. I. & Saleem, M., 2 Dec 2021, In: Communications Biology. 4, 1, 1351.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile2 Downloads (Pure)
Lay, A. C., Barrington, A. F., Hurcombe, J. A., Ramnath, R. D., Graham, M., Lewis, P. A., Wilson, M. C., Heesom, K. J., Butler, M. J., Perrett, R. M., Neal, C. R., Herbert, E., Mountjoy, E., Atan, D., Nair, V., Ju, W., Nelson, R. G., Kretzler, M., Satchell, S. C., McArdle, C. A. & 2 others, , 19 Jun 2020, (E-pub ahead of print) In: Proceedings of the National Academy of Sciences of the United States of America. 117, 27, p. 15862-15873 12 p., 202004651.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile39 Downloads (Pure)
Cystatin C and alpha-1-Microglobulin Predict Severe Acute Kidney Injury in Patients with Hemorrhagic Fever with Renal SyndromeHansson, M. J., Gustafsson, R., Jacquet, C., Chebaane, N., Satchell, S. C., Thunberg, T., Ahlm, C. & Fors Connolly, A-M., 18 Aug 2020, In: Pathogens. 9, 8, 14 p., 666.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile4 Citations (Scopus)19 Downloads (Pure)