Publications by authors named "K R Lemley"
Article Synopsis
- - Fasting-mimicking diets (FMD), specifically a low-salt version (LS-FMD), were tested in rats with kidney damage and were found to restore normal kidney function and structure by inducing a nephrogenic gene program.
- - LS-FMD activated pathways that promote cell reprogramming in the kidney, specifically targeting podocytes, which play a critical role in kidney health.
- - A pilot study in patients with chronic kidney disease showed that FMD cycles improved kidney function and reduced protein levels in urine, indicating potential for further research in treating progressive kidney diseases.
Here, we used digital spatial profiling (DSP) to describe the glomerular transcriptomic signatures that may characterize the complex molecular mechanisms underlying progressive kidney disease in Alport syndrome, focal segmental glomerulosclerosis, and membranous nephropathy. Our results revealed significant transcriptional heterogeneity among diseased glomeruli, and this analysis showed that histologically similar glomeruli manifested different transcriptional profiles. Using glomerular pathology scores to establish an axis of progression, we identified molecular pathways with progressively decreased expression in response to increasing pathology scores, including signal recognition particle-dependent cotranslational protein targeting to membrane and selenocysteine synthesis pathways.
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- Antipodocyte autoantibodies cause primary membranous nephropathy (MN), a leading cause of nephrotic syndrome, and this was modeled using a glomerulus-on-a-chip system with anti-PLA2R antibodies.
- The study found that MN serum exposure led to harmful IgG deposition and complement activation on podocytes, decreasing their ability to filter albumin, but blocking C3aR reduced this oxidative stress and leakage.
- C3aR antagonism not only mitigated damage in vitro but also prevented proteinuria in a mouse model, highlighting C3a/C3aR signaling as a potential new treatment target for MN.