A Microfluidic Platform for Investigating Transmembrane Pressure-Induced Glomerular Leakage
Transmembrane pressure across the glomerular filter barrier may underlie renal failure. However, studies of renal failure have been difficult owing to a lack of in vitro models to capture the transmembrane pressure in a controlled approach. Here we report a microfluidic platform of podocyte culture...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2018-05-01
|
Series: | Micromachines |
Subjects: | |
Online Access: | http://www.mdpi.com/2072-666X/9/5/228 |
id |
doaj-80c8455cbd7c4f0493408d7cca7274df |
---|---|
record_format |
Article |
spelling |
doaj-80c8455cbd7c4f0493408d7cca7274df2020-11-24T23:14:22ZengMDPI AGMicromachines2072-666X2018-05-019522810.3390/mi9050228mi9050228A Microfluidic Platform for Investigating Transmembrane Pressure-Induced Glomerular LeakageTing-Hsuan Chen0Jie-Sheng Chen1Yi-Ching Ko2Jyun-Wei Chen3Hsueh-Yao Chu4Chih-Shuan Lu5Chiao-Wen Chu6Hsiang-Hao Hsu7Fan-Gang Tseng8Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong, ChinaDepartment of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan 33305, TaiwanDepartment of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, TaiwanInstitute of Nano Engineering and Microsystems, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan 33305, TaiwanDepartment of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, TaiwanTransmembrane pressure across the glomerular filter barrier may underlie renal failure. However, studies of renal failure have been difficult owing to a lack of in vitro models to capture the transmembrane pressure in a controlled approach. Here we report a microfluidic platform of podocyte culture to investigate transmembrane pressure induced glomerular leakage. Podocytes, the glomerular epithelial cells essential for filtration function, were cultivated on a porous membrane supplied with transmembrane pressure ΔP. An anodic aluminum oxide membrane with collagen coating was used as the porous membrane, and the filtration function was evaluated using dextrans of different sizes. The results show that dextran in 20 kDa and 70 kDa can penetrate the podocyte membrane, whereas dextran in 500 kDa was blocked until ΔP ≥ 60 mmHg, which resembles the filtration function when ΔP was in the range of a healthy kidney (ΔP < 60 mmHg) as well as the hypertension-induced glomerular leakage (ΔP ≥ 60 mmHg). Additionally, analysis showed that synaptopodin and actin were also downregulated when ΔP > 30 mmHg, indicating that the dysfunction of renal filtration is correlated with the reduction of synaptopodin expression and disorganized actin cytoskeleton. Taking together, our microfluidic platform enables the investigation of transmembrane pressure in glomerular filter membrane, with potential implications for drug development in the future.http://www.mdpi.com/2072-666X/9/5/228podocytesglomerular leakagetransmembrane pressuremicrofluidics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ting-Hsuan Chen Jie-Sheng Chen Yi-Ching Ko Jyun-Wei Chen Hsueh-Yao Chu Chih-Shuan Lu Chiao-Wen Chu Hsiang-Hao Hsu Fan-Gang Tseng |
spellingShingle |
Ting-Hsuan Chen Jie-Sheng Chen Yi-Ching Ko Jyun-Wei Chen Hsueh-Yao Chu Chih-Shuan Lu Chiao-Wen Chu Hsiang-Hao Hsu Fan-Gang Tseng A Microfluidic Platform for Investigating Transmembrane Pressure-Induced Glomerular Leakage Micromachines podocytes glomerular leakage transmembrane pressure microfluidics |
author_facet |
Ting-Hsuan Chen Jie-Sheng Chen Yi-Ching Ko Jyun-Wei Chen Hsueh-Yao Chu Chih-Shuan Lu Chiao-Wen Chu Hsiang-Hao Hsu Fan-Gang Tseng |
author_sort |
Ting-Hsuan Chen |
title |
A Microfluidic Platform for Investigating Transmembrane Pressure-Induced Glomerular Leakage |
title_short |
A Microfluidic Platform for Investigating Transmembrane Pressure-Induced Glomerular Leakage |
title_full |
A Microfluidic Platform for Investigating Transmembrane Pressure-Induced Glomerular Leakage |
title_fullStr |
A Microfluidic Platform for Investigating Transmembrane Pressure-Induced Glomerular Leakage |
title_full_unstemmed |
A Microfluidic Platform for Investigating Transmembrane Pressure-Induced Glomerular Leakage |
title_sort |
microfluidic platform for investigating transmembrane pressure-induced glomerular leakage |
publisher |
MDPI AG |
series |
Micromachines |
issn |
2072-666X |
publishDate |
2018-05-01 |
description |
Transmembrane pressure across the glomerular filter barrier may underlie renal failure. However, studies of renal failure have been difficult owing to a lack of in vitro models to capture the transmembrane pressure in a controlled approach. Here we report a microfluidic platform of podocyte culture to investigate transmembrane pressure induced glomerular leakage. Podocytes, the glomerular epithelial cells essential for filtration function, were cultivated on a porous membrane supplied with transmembrane pressure ΔP. An anodic aluminum oxide membrane with collagen coating was used as the porous membrane, and the filtration function was evaluated using dextrans of different sizes. The results show that dextran in 20 kDa and 70 kDa can penetrate the podocyte membrane, whereas dextran in 500 kDa was blocked until ΔP ≥ 60 mmHg, which resembles the filtration function when ΔP was in the range of a healthy kidney (ΔP < 60 mmHg) as well as the hypertension-induced glomerular leakage (ΔP ≥ 60 mmHg). Additionally, analysis showed that synaptopodin and actin were also downregulated when ΔP > 30 mmHg, indicating that the dysfunction of renal filtration is correlated with the reduction of synaptopodin expression and disorganized actin cytoskeleton. Taking together, our microfluidic platform enables the investigation of transmembrane pressure in glomerular filter membrane, with potential implications for drug development in the future. |
topic |
podocytes glomerular leakage transmembrane pressure microfluidics |
url |
http://www.mdpi.com/2072-666X/9/5/228 |
work_keys_str_mv |
AT tinghsuanchen amicrofluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT jieshengchen amicrofluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT yichingko amicrofluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT jyunweichen amicrofluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT hsuehyaochu amicrofluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT chihshuanlu amicrofluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT chiaowenchu amicrofluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT hsianghaohsu amicrofluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT fangangtseng amicrofluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT tinghsuanchen microfluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT jieshengchen microfluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT yichingko microfluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT jyunweichen microfluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT hsuehyaochu microfluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT chihshuanlu microfluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT chiaowenchu microfluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT hsianghaohsu microfluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage AT fangangtseng microfluidicplatformforinvestigatingtransmembranepressureinducedglomerularleakage |
_version_ |
1725594716188180480 |