Matches in SemOpenAlex for { <https://semopenalex.org/work/W3045585980> ?p ?o ?g. }
- W3045585980 abstract "Kidney glomerulosclerosis commonly progresses to end-stage kidney failure, but pathogenic mechanisms are still poorly understood. Here, we show that podocyte expression of decay-accelerating factor (DAF/CD55), a complement C3 convertase regulator, crucially controls disease in murine models of adriamycin (ADR)-induced focal and segmental glomerulosclerosis (FSGS) and streptozotocin (STZ)-induced diabetic glomerulosclerosis. ADR induces enzymatic cleavage of DAF from podocyte surfaces, leading to complement activation. C3 deficiency or prevention of C3a receptor (C3aR) signaling abrogates disease despite DAF deficiency, confirming complement dependence. Mechanistic studies show that C3a/C3aR ligations on podocytes initiate an autocrine IL-1β/IL-1R1 signaling loop that reduces nephrin expression, causing actin cytoskeleton rearrangement. Uncoupling IL-1β/IL-1R1 signaling prevents disease, providing a causal link. Glomeruli of patients with FSGS lack DAF and stain positive for C3d, and urinary C3a positively correlates with the degree of proteinuria. Together, our data indicate that the development and progression of glomerulosclerosis involve loss of podocyte DAF, triggering local, complement-dependent, IL-1β-induced podocyte injury, potentially identifying new therapeutic targets." @default.
- W3045585980 created "2020-08-03" @default.
- W3045585980 creator A5002941103 @default.
- W3045585980 creator A5004076571 @default.
- W3045585980 creator A5004877715 @default.
- W3045585980 creator A5005075162 @default.
- W3045585980 creator A5013847820 @default.
- W3045585980 creator A5015826182 @default.
- W3045585980 creator A5025947755 @default.
- W3045585980 creator A5029752591 @default.
- W3045585980 creator A5031943687 @default.
- W3045585980 creator A5035400589 @default.
- W3045585980 creator A5035791401 @default.
- W3045585980 creator A5038810361 @default.
- W3045585980 creator A5041424817 @default.
- W3045585980 creator A5050681620 @default.
- W3045585980 creator A5051235984 @default.
- W3045585980 creator A5051543594 @default.
- W3045585980 creator A5055261107 @default.
- W3045585980 creator A5056348156 @default.
- W3045585980 creator A5056491417 @default.
- W3045585980 creator A5059167580 @default.
- W3045585980 creator A5060385446 @default.
- W3045585980 creator A5064989188 @default.
- W3045585980 creator A5070520914 @default.
- W3045585980 creator A5072780668 @default.
- W3045585980 creator A5083498619 @default.
- W3045585980 creator A5088980123 @default.
- W3045585980 date "2020-07-27" @default.
- W3045585980 modified "2023-10-09" @default.
- W3045585980 title "Loss of decay-accelerating factor triggers podocyte injury and glomerulosclerosis" @default.
- W3045585980 cites W1515505902 @default.
- W3045585980 cites W1516284454 @default.
- W3045585980 cites W1529920848 @default.
- W3045585980 cites W1533678663 @default.
- W3045585980 cites W1561068209 @default.
- W3045585980 cites W1636793459 @default.
- W3045585980 cites W1680336919 @default.
- W3045585980 cites W1845314465 @default.
- W3045585980 cites W1865928485 @default.
- W3045585980 cites W1979144815 @default.
- W3045585980 cites W1993159760 @default.
- W3045585980 cites W1995233835 @default.
- W3045585980 cites W2005759195 @default.
- W3045585980 cites W2009109782 @default.
- W3045585980 cites W2012833251 @default.
- W3045585980 cites W2018920164 @default.
- W3045585980 cites W2019234906 @default.
- W3045585980 cites W2021988356 @default.
- W3045585980 cites W2036692587 @default.
- W3045585980 cites W2044748328 @default.
- W3045585980 cites W2048437702 @default.
- W3045585980 cites W2049628599 @default.
- W3045585980 cites W2050103347 @default.
- W3045585980 cites W2065757191 @default.
- W3045585980 cites W2072361327 @default.
- W3045585980 cites W2072802709 @default.
- W3045585980 cites W2075703072 @default.
- W3045585980 cites W2076848429 @default.
- W3045585980 cites W2077144266 @default.
- W3045585980 cites W2083175247 @default.
- W3045585980 cites W2086590742 @default.
- W3045585980 cites W2088128266 @default.
- W3045585980 cites W2095759316 @default.
- W3045585980 cites W2097655989 @default.
- W3045585980 cites W2102307463 @default.
- W3045585980 cites W2104199760 @default.
- W3045585980 cites W2108373994 @default.
- W3045585980 cites W2113036981 @default.
- W3045585980 cites W2122835088 @default.
- W3045585980 cites W2137997062 @default.
- W3045585980 cites W2138002856 @default.
- W3045585980 cites W2139620102 @default.
- W3045585980 cites W2140733306 @default.
- W3045585980 cites W2142364904 @default.
- W3045585980 cites W2144489880 @default.
- W3045585980 cites W2148652246 @default.
- W3045585980 cites W2154396050 @default.
- W3045585980 cites W2155571650 @default.
- W3045585980 cites W2157230648 @default.
- W3045585980 cites W2164060244 @default.
- W3045585980 cites W2168450345 @default.
- W3045585980 cites W2168465695 @default.
- W3045585980 cites W2169570354 @default.
- W3045585980 cites W2405183840 @default.
- W3045585980 cites W2408455775 @default.
- W3045585980 cites W2462483854 @default.
- W3045585980 cites W2468199092 @default.
- W3045585980 cites W2510768527 @default.
- W3045585980 cites W2594651069 @default.
- W3045585980 cites W2618245942 @default.
- W3045585980 cites W2624798972 @default.
- W3045585980 cites W2724335952 @default.
- W3045585980 cites W2733091118 @default.
- W3045585980 cites W2763552419 @default.
- W3045585980 cites W2791851267 @default.
- W3045585980 cites W2792416359 @default.
- W3045585980 cites W2794018905 @default.
- W3045585980 cites W2794282972 @default.
- W3045585980 cites W2804994040 @default.