Cardiotrophin‐1 therapy reduces disease severity in a murine model of glomerular disease

• DOI: 10.14814/phy2.16129
• Publication Date: 2024-07-03T02:00:17Z
• Authors: Nuria Perretta‐Te...; Karen L. Price; Daniyal J. Jafree; Gideon Pomeranz; Maria Kolatsi‐Joa...; Carlos Martínez‐S...; David A. Long; Elisavet Vasilopo...
• Keywords: Male; Physiology; fibrosis; Kidney Glomerulus; glomerulus; Fibrosis; cardiotrophin‐1; Mice, Inbred C57BL; Mice; Disease Models, Animal; Glomerulonephritis; inflammation; QP1-981; Animals; Cytokines; Humans; Original Article

Abstract Cardiotrophin‐1 (CT‐1), a member of the interleukin (IL)‐6 cytokine family, has renoprotective effects in mouse models acute kidney disease and tubulointerstitial fibrosis, but its role glomerular is unknown. To address this, we used model nephrotoxic nephritis to test hypothesis that CT‐1 also protective immune‐mediated disease. Using immunohistochemistry analysis single‐cell RNA‐sequencing data isolated glomeruli, demonstrate expressed glomerulus male mice, predominantly parietal epithelial cells downregulated mice with nephritis. Furthermore, from patients revealed human associated reduced transcript levels. In established proteinuria, administration resulted albuminuria, prevented podocyte loss, sustained plasma creatinine, compared administered saline. treatment fibrosis cortex, peri‐glomerular macrophage accumulation levels pro‐inflammatory mediator complement component 5a. conclusion, intervention therapy delays progression by preserving function inhibiting renal inflammation fibrosis.