Perretta-Tejedor, N;
Price, KL;
Jafree, DJ;
Pomeranz, G;
Kolatsi-Joannou, M;
Martinez-Salgado, C;
Long, DA;
(2024)
Cardiotrophin-1 therapy reduces disease severity in a murine model of glomerular disease.
Physiological Reports
, 12
(13)
, Article e16129. 10.14814/phy2.16129.
Preview |
Text
Long_Physiological Reports - 2024 - P).pdf Download (8MB) | Preview |
Abstract
Cardiotrophin-1 (CT-1), a member of the interleukin (IL)-6 cytokine family, has renoprotective effects in mouse models of acute kidney disease and tubulointerstitial fibrosis, but its role in glomerular disease is unknown. To address this, we used the mouse model of nephrotoxic nephritis to test the hypothesis that CT-1 also has a protective role in immune-mediated glomerular disease. Using immunohistochemistry and analysis of single-cell RNA-sequencing data of isolated glomeruli, we demonstrate that CT-1 is expressed in the glomerulus in male mice, predominantly in parietal epithelial cells and is downregulated in mice with nephrotoxic nephritis. Furthermore, analysis of data from patients revealed that human glomerular disease is also associated with reduced glomerular CT-1 transcript levels. In male mice with nephrotoxic nephritis and established proteinuria, administration of CT-1 resulted in reduced albuminuria, prevented podocyte loss, and sustained plasma creatinine, compared with mice administered saline. CT-1 treatment also reduced fibrosis in the kidney cortex, peri-glomerular macrophage accumulation and the kidney levels of the pro-inflammatory mediator complement component 5a. In conclusion, CT-1 intervention therapy delays the progression of glomerular disease in mice by preserving kidney function and inhibiting renal inflammation and fibrosis.
| Type: | Article |
|---|---|
| Title: | Cardiotrophin-1 therapy reduces disease severity in a murine model of glomerular disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.14814/phy2.16129 |
| Publisher version: | https://doi.org/10.14814/phy2.16129 |
| Language: | English |
| Additional information: | © 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | cardiotrophin-1, fibrosis, glomerulus, inflammation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10194017 |
Archive Staff Only
 |
View Item |
