Kim, Jaehoon Kim, Hyunho Kang, Jeong Suk Lee, Eun Soo Chung, Choon Hee Oh, Hyun Jeong Kim, YongTae Chung, Seok Lee, Eun Young 2024-01-19T09:02:42Z 2024-01-19T09:02:42Z 2023-08-02 2023-08 1473-0197 https://pubs.kist.re.kr/handle/201004/113437 In vitro investigation of a glomerular filtration barrier (GFB) remains difficult because of the inability to mimic its specialized structure, although various kidney diseases are characterized by GFB dysfunction. Here, the development of a microfluidic model that replicates the physiology of the GFB has been achieved by tunable glomerular basement membrane (gBM) deposition and 3D co-culture of podocytes with glomerular endothelial cells (gECs). By precisely controlling the thickness of the gBM, our model successfully reproduced the biphasic response of the GFB, where variations in gBM thickness influence barrier properties. Moreover, this microscale proximity of gECs and podocytes facilitated their dynamic crosstalk, which is essential for maintaining the integrity and function of the GFB. We observed that addition of gBM and podocytes enhanced barrier function of gECs by inducing up-regulation of gEC's tight junctions synergistically, and moreover, found an ultrastructure of gECs-gBM-podocytes' foot process contacting each other by confocal and TEM imaging. The dynamic interaction of gECs and podocytes played a significant role in the response to drug-induced injury and the regulation of barrier properties. Nephrotoxic injury simulated in our model helped to elucidate that the over-production of vascular endothelial growth factor A from the injured podocytes mediates GFB impairment. We believe that our GFB model can provide a valuable tool for mechanistic studies such as investigating GFB biology, comprehending disease mechanisms, and evaluating potential therapeutic approaches in a controlled and physiologically relevant environment. English Royal Society of Chemistry Glomerular filtration barrier modeling on a chip with tunable basement membrane deposition and 3D cultured podocytes Article 10.1039/d3lc00147d 1 Lab on a Chip, v.23, no.15, pp.3501 - 3517 Lab on a Chip 23 15 3501 3517 N scie scopus 001025973100001 Biochemical Research Methods Chemistry, Multidisciplinary Chemistry, Analytical Nanoscience & Nanotechnology Instruments & Instrumentation Biochemistry & Molecular Biology Chemistry Science & Technology - Other Topics Instruments & Instrumentation Article DIABETIC-NEPHROPATHY VEGF EXPRESSION INJURY ENDOTHELIUM MECHANISMS BLOCKADE MOTILITY CHANNEL DISEASE