A Review of Podocyte Biology

被引:203
作者
Garg, Puneet [1 ]
机构
[1] Univ Michigan, Dept Internal Med, Div Nephrol, 1150 W Med Ctr Dr,1560 MSRB 2, Ann Arbor, MI 48109 USA
关键词
Renal glomerulus; Podocytes; Actin; Nephrin; Adhesion; Signaling; Proteinuria; Nephrotic syndrome; Therapeutic targets; RESISTANT NEPHROTIC SYNDROME; PROTEINURIC KIDNEY-DISEASE; FOOT PROCESS EFFACEMENT; SEGMENTAL GLOMERULOSCLEROSIS; ACTIN POLYMERIZATION; GLOMERULAR-DISEASE; CELL-MIGRATION; SLIT DIAPHRAGM; NEPHRIN; ADHESION;
D O I
10.1159/000481633
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background: Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature of multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked to mechanistic dysfunctions in the renal glomerulus involving the function of podocyte epithelial cells, including podocyte foot process effacement. Summary: Developments in imaging technology are improving knowledge of the detailed structure of the human renal glomerulus and cortex. Podocyte foot processes attach themselves to the glomerular capillaries at the glomerular basement membrane (GBM) forming intercellular junctions that form slit diaphragm filtration barriers that help maintain normal renal function. Damage in this area has been implicated in glomerular disease. Injured podocytes undergo effacement whereby they lose their structure and spread out, leading to a reduction in filtration barrier function. Effacement is typically associated with the presence of proteinuria in focal segmental glomerulosclerosis, minimal change disease, and diabetes. It is thought to be due to a breakdown in the actin cytoskeleton of the foot processes, complex contractile apparatuses that allow podocytes to dynamically reorganize according to changes in filtration requirements. The process of podocyte depletion correlates with the development of glomerular sclerosis and chronic kidney disease. Focal adhesion complexes that interact with the underlying GBM bind the podocytes within the glomerular structure and prevent their detachment. Key Messages: Knowledge of glomerular podocyte biology is helping to advance our understanding of the science and mechanics of the glomerular filtering process, opening the way to a variety of new potential applications for clinical targeting. (C) 2018 S. Karger AG, Basel
引用
收藏
页码:3 / 13
页数:11
相关论文
共 49 条
  • [1] Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis
    Akilesh, Shreeram
    Suleiman, Hani
    Yu, Haiyang
    Stander, M. Christine
    Lavin, Peter
    Gbadegesin, Rasheed
    Antignac, Corinne
    Pollak, Martin
    Kopp, Jeffrey B.
    Winn, Michelle P.
    Shaw, Andrey S.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (10) : 4127 - 4137
  • [2] Aoudjit Lamine, 2011, J Signal Transduct, V2011, P376543, DOI 10.1155/2011/376543
  • [3] Motor Protein Myo1c Is a Podocyte Protein That Facilitates the Transport of Slit Diaphragm Protein Neph1 to the Podocyte Membrane
    Arif, E.
    Wagner, M. C.
    Johnstone, D. B.
    Wong, H. N.
    George, B.
    Pruthi, P. A.
    Lazzara, M. J.
    Nihalani, D.
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2011, 31 (10) : 2134 - 2150
  • [4] Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling
    Asanuma, K
    Yanagida-Asanuma, E
    Faul, C
    Tomino, Y
    Kim, K
    Mundel, P
    [J]. NATURE CELL BIOLOGY, 2006, 8 (05) : 485 - U109
  • [5] Synaptopodin Is a Coincidence Detector of Tyrosine versus Serine/Threonine Phosphorylation for the Modulation of Rho Protein Crosstalk in Podocytes
    Buvall, Lisa
    Wallentin, Hanna
    Sieber, Jonas
    Andreeva, Svetlana
    Choi, Hoon Young
    Mundel, Peter
    Greka, Anna
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2017, 28 (03): : 837 - 851
  • [6] Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis
    Daehn, Ilse
    Casalena, Gabriella
    Zhang, Taoran
    Shi, Shaolin
    Fenninger, Franz
    Barasch, Nicholas
    Yu, Liping
    D'Agati, Vivette
    Schlondorff, Detlef
    Kriz, Wilhelm
    Haraldsson, Borje
    Bottinger, Erwin P.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (04) : 1608 - 1621
  • [7] Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases
    Eremina, V
    Sood, M
    Haigh, J
    Nagy, A
    Lajoie, G
    Ferrara, N
    Gerber, HP
    Kikkawa, Y
    Miner, JH
    Quaggin, SE
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (05) : 707 - 716
  • [8] Vascular endothelial growth factor A signaling in the podocyte-endothelial compartment is required for mesangial cell migration and survival
    Eremina, Vera
    Cui, Shiying
    Gerber, Hanspeter
    Ferrara, Napoleone
    Haigh, Jody
    Nagy, Andras
    Ema, Masatsugu
    Rossant, Janet
    Jothy, Serge
    Miner, Jeffrey H.
    Quaggin, Susan E.
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (03): : 724 - 735
  • [9] Growth-Dependent Podocyte Failure Causes Glomerulosclerosis
    Fukuda, Akihiro
    Chowdhury, Mahboob A.
    Venkatareddy, Madhusudan P.
    Wang, Su Q.
    Nishizono, Ryuzoh
    Suzuki, Tsukasa
    Wickman, Larysa T.
    Wiggins, Jocelyn E.
    Muchayi, Timothy
    Fingar, Diane
    Shedden, Kerby A.
    Inoki, Ken
    Wiggins, Roger C.
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2012, 23 (08): : 1351 - 1363
  • [10] Nephrin and Podocin functions are highly conserved between the zebrafish pronephros and mammalian metanephros
    Fukuyo, Yayoi
    Nakamura, Tomomi
    Bubenshchikova, Ekaterina
    Powell, Rebecca
    Tsuji, Takashi
    Janknecht, Ralf
    Obara, Tomoko
    [J]. MOLECULAR MEDICINE REPORTS, 2014, 9 (02) : 457 - 465