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Albumin-associated free fatty acids induce macropinocytosis in podocytes

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Albumin-associated free fatty acids induce macropinocytosis in podocytes. / Chung, Jun-Jae; Huber, Tobias B; Gödel, Markus; Jarad, George; Hartleben, Björn; Kwoh, Christopher; Keil, Alexander; Karpitskiy, Aleksey; Hu, Jiancheng; Huh, Christine J; Cella, Marina; Gross, Richard W; Miner, Jeffrey H; Shaw, Andrey S.

In: J CLIN INVEST, Vol. 125, No. 6, 06.2015, p. 2307-16.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Chung, J-J, Huber, TB, Gödel, M, Jarad, G, Hartleben, B, Kwoh, C, Keil, A, Karpitskiy, A, Hu, J, Huh, CJ, Cella, M, Gross, RW, Miner, JH & Shaw, AS 2015, 'Albumin-associated free fatty acids induce macropinocytosis in podocytes', J CLIN INVEST, vol. 125, no. 6, pp. 2307-16. https://doi.org/10.1172/JCI79641

APA

Chung, J-J., Huber, T. B., Gödel, M., Jarad, G., Hartleben, B., Kwoh, C., Keil, A., Karpitskiy, A., Hu, J., Huh, C. J., Cella, M., Gross, R. W., Miner, J. H., & Shaw, A. S. (2015). Albumin-associated free fatty acids induce macropinocytosis in podocytes. J CLIN INVEST, 125(6), 2307-16. https://doi.org/10.1172/JCI79641

Vancouver

Chung J-J, Huber TB, Gödel M, Jarad G, Hartleben B, Kwoh C et al. Albumin-associated free fatty acids induce macropinocytosis in podocytes. J CLIN INVEST. 2015 Jun;125(6):2307-16. https://doi.org/10.1172/JCI79641

Bibtex

@article{0d9312b147ce40fcba7f70366ddcc3b6,
title = "Albumin-associated free fatty acids induce macropinocytosis in podocytes",
abstract = "Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. Nephrotic syndrome results from a breakdown of the kidney filtration barrier and is associated with proteinuria, hyperlipidemia, and edema. Additionally, podocytes undergo changes in morphology and internalize plasma proteins in response to this disorder. Here, we used fluid-phase tracers in murine models and determined that podocytes actively internalize fluid from the plasma and that the rate of internalization is increased when the filtration barrier is disrupted. In cultured podocytes, the presence of free fatty acids (FFAs) associated with serum albumin stimulated macropinocytosis through a pathway that involves FFA receptors, the Gβ/Gγ complex, and RAC1. Moreover, mice with elevated levels of plasma FFAs as the result of a high-fat diet were more susceptible to Adriamycin-induced proteinuria than were animals on standard chow. Together, these results support a model in which podocytes sense the disruption of the filtration barrier via FFAs bound to albumin and respond by enhancing fluid-phase uptake. The response to FFAs may function in the development of nephrotic syndrome by amplifying the effects of proteinuria.",
keywords = "Albumins, Animals, Antibiotics, Antineoplastic, Cell Line, Transformed, Dietary Fats, Doxorubicin, Fatty Acids, Mice, Mice, Inbred BALB C, Mice, Knockout, Nephrotic Syndrome, Neuropeptides, Pinocytosis, Podocytes, Proteinuria, rac1 GTP-Binding Protein, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Jun-Jae Chung and Huber, {Tobias B} and Markus G{\"o}del and George Jarad and Bj{\"o}rn Hartleben and Christopher Kwoh and Alexander Keil and Aleksey Karpitskiy and Jiancheng Hu and Huh, {Christine J} and Marina Cella and Gross, {Richard W} and Miner, {Jeffrey H} and Shaw, {Andrey S}",
year = "2015",
month = jun,
doi = "10.1172/JCI79641",
language = "English",
volume = "125",
pages = "2307--16",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

RIS

TY - JOUR

T1 - Albumin-associated free fatty acids induce macropinocytosis in podocytes

AU - Chung, Jun-Jae

AU - Huber, Tobias B

AU - Gödel, Markus

AU - Jarad, George

AU - Hartleben, Björn

AU - Kwoh, Christopher

AU - Keil, Alexander

AU - Karpitskiy, Aleksey

AU - Hu, Jiancheng

AU - Huh, Christine J

AU - Cella, Marina

AU - Gross, Richard W

AU - Miner, Jeffrey H

AU - Shaw, Andrey S

PY - 2015/6

Y1 - 2015/6

N2 - Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. Nephrotic syndrome results from a breakdown of the kidney filtration barrier and is associated with proteinuria, hyperlipidemia, and edema. Additionally, podocytes undergo changes in morphology and internalize plasma proteins in response to this disorder. Here, we used fluid-phase tracers in murine models and determined that podocytes actively internalize fluid from the plasma and that the rate of internalization is increased when the filtration barrier is disrupted. In cultured podocytes, the presence of free fatty acids (FFAs) associated with serum albumin stimulated macropinocytosis through a pathway that involves FFA receptors, the Gβ/Gγ complex, and RAC1. Moreover, mice with elevated levels of plasma FFAs as the result of a high-fat diet were more susceptible to Adriamycin-induced proteinuria than were animals on standard chow. Together, these results support a model in which podocytes sense the disruption of the filtration barrier via FFAs bound to albumin and respond by enhancing fluid-phase uptake. The response to FFAs may function in the development of nephrotic syndrome by amplifying the effects of proteinuria.

AB - Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. Nephrotic syndrome results from a breakdown of the kidney filtration barrier and is associated with proteinuria, hyperlipidemia, and edema. Additionally, podocytes undergo changes in morphology and internalize plasma proteins in response to this disorder. Here, we used fluid-phase tracers in murine models and determined that podocytes actively internalize fluid from the plasma and that the rate of internalization is increased when the filtration barrier is disrupted. In cultured podocytes, the presence of free fatty acids (FFAs) associated with serum albumin stimulated macropinocytosis through a pathway that involves FFA receptors, the Gβ/Gγ complex, and RAC1. Moreover, mice with elevated levels of plasma FFAs as the result of a high-fat diet were more susceptible to Adriamycin-induced proteinuria than were animals on standard chow. Together, these results support a model in which podocytes sense the disruption of the filtration barrier via FFAs bound to albumin and respond by enhancing fluid-phase uptake. The response to FFAs may function in the development of nephrotic syndrome by amplifying the effects of proteinuria.

KW - Albumins

KW - Animals

KW - Antibiotics, Antineoplastic

KW - Cell Line, Transformed

KW - Dietary Fats

KW - Doxorubicin

KW - Fatty Acids

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Knockout

KW - Nephrotic Syndrome

KW - Neuropeptides

KW - Pinocytosis

KW - Podocytes

KW - Proteinuria

KW - rac1 GTP-Binding Protein

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1172/JCI79641

DO - 10.1172/JCI79641

M3 - SCORING: Journal article

C2 - 25915582

VL - 125

SP - 2307

EP - 2316

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 6

ER -