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Abstract The glomerular filtration barrier (GFB) filters the blood to remove toxins while retaining high molecular weight proteins in the circulation. The glomerular basement membrane (GBM) and podocytes, highly specialized epithelial cells, are critical components of the filtration barrier. The GBM serves as a physical barrier to passage of molecules into the filtrate. Podocytes adhere to the filtrate side of the GBM and further restrict passage of high molecular weight molecules into the filtrate. Here, a 3D cell culture model of the glomerular filtration barrier to evaluate the role of the GBM and podocytes in mediating molecular diffusion is developed. GBM is isolated from mammalian kidneys to recapitulate the composition and mechanics of the in vivo basement membrane. The GFB model exhibits molecular selectivity that is comparable to the in vivo filtration barrier. The GBM alone provides a stringent barrier to passage of albumin and Ficoll. Podocytes further restrict molecular diffusion. Damage to the GBM that is typical of diabetic kidney disease is simulated using hypochlorous acid and results in increased molecular diffusion. This system can serve as a platform to evaluate the effects of GBM damage, podocyte injury, and reciprocal effects of altered podocyte–GBM interactions on kidney microvascular permeability.
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This content will become publicly available on July 1, 2026
Logic-based modeling of inflammatory macrophage cross talk with glomerular endothelial cells in diabetic kidney disease
This work provides a novel analysis of signaling cross talk between macrophages and glomerular endothelial cells in the early stage of diabetic kidney disease. A logic-based mathematical modeling approach identified vital signaling molecules and interactions that regulate glucose-mediated inflammation in glomerular endothelial cells and cause endothelial dysfunction in the diabetic kidney. Simulated interactions among vascular endothelial growth factor receptor 1, nitric oxide, and calcium significantly affected the intercellular junction proteins between glomerular endothelial cells.
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- Award ID(s):
- 2133411
- PAR ID:
- 10628327
- Publisher / Repository:
- American Physiological Society
- Date Published:
- Journal Name:
- American Journal of Physiology-Renal Physiology
- Volume:
- 329
- Issue:
- 1
- ISSN:
- 1931-857X
- Page Range / eLocation ID:
- F202 to F224
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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