Asymmetric origins of the mature glomerular basement membrane

Journal of Cellular Physiology - Tập 157 Số 1 - Trang 169-177 - 1993
Larry K. Lee1, Allan S. Pollock1, David H. Lovett1
1The Medical Service, San Francisco VAMC/University of California, San Francisco, California 94121

Tóm tắt

AbstractRenal plasma filtration is a critical physiologic function that depends upon the precise composition and arrangement of the constituent extracellular matrix proteins within the glomerular basement membrane (GBM). The GBM develops during renal embryogenesis by the fusion of discrete basement membranes produced independently by endothelial and visceral epithelial cells, and, possibly from matrix secreted by the mesangial cells. In the mature animal, however, the epithelial cell has generally been accepted as the sole source of all GBM constituent proteins. Although the final structures and distributions of the component proteins have been defined by histochemical techniques, the individual contributions of the three resident glomerular cell types to the maintenance and turnover of the mature GBM remain uncertain. We report the application of a new technique, in situ reverse transcription (ISRT), for the localization of RNA transcripts of nine major GBM protein components within the closely apposed cells of the glomerulus. Using this technique, we demonstrate that in normal adult rat glomeruli the RNA transcripts for heparan sulfate proteoglycan and the laminin‐S chain are primarily expressed by visceral epithelial cells, while Type IV α‐1 and α‐2 collagen transcripts were restricted to the endothelial cells in a heterogeneous pattern. RNA transcripts for entactin and the laminin‐A and ‐B2 chains were expressed by all three glomerular cell types, while laminin‐B1 and fibronectin transcripts were limited to the mesangium. These findings demonstrate that GBM synthesis in the mature animal is not restricted to the epithelial cell and that all intrinsic glomerular cells contribute to the production of GBM protein components. The ISRT technique also provided the additional, and unexpected, finding that appreciable synthetic heterogeneity exists within individual glomerular cell types. © 1993 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1083/jcb.100.6.1988

10.1002/path.1711490402

10.1177/34.7.3519749

10.1084/jem.115.5.929

10.1038/ki.1990.198

10.1016/0003-9861(89)90143-4

10.1016/S0021-9258(18)47648-X

10.1038/ki.1989.110

10.1083/jcb.87.3.691

10.1093/nar/15.6.2772

10.1177/37.6.2723404

10.1083/jcb.113.3.689

Desjardins M., 1990, Heterogeneous distribution of monomeric elements from the globular domain (NC1) of type IV collagen in renal basement membranes as revealed by high resolution quantitative immunocytochemistry, Lab. Invest., 63, 637

10.1007/978-1-4615-3770-0_12

10.1038/ki.1992.42

Foidart J. M., 1980, Synthesis of collagen and fibronectin by glomerular cells in culture, Renal Physiol., 3, 183

10.1007/BF00197212

10.1177/36.3.2963856

10.1083/jcb.108.4.1567

10.1016/0012-1606(78)90094-5

10.1073/pnas.87.4.1606

10.1073/pnas.73.7.2361

10.1038/ki.1992.120

10.1172/JCI114454

10.1073/pnas.76.3.1303

10.1083/jcb.86.2.688

10.1038/ki.1991.256

10.1073/pnas.76.7.3518

10.1021/bi00350a005

Kleppel M. M., 1989, Distribution of familial nephritis antigen in normal tissue and renal basement membranes of patients with homozygous and heterozygous Alport familial nephritis: Relationship of familial nephritis and Goodpasture antigens to novel collagen chains and Type IV collagen, Lab. Invest., 61, 278

10.1038/ki.1984.89

10.1042/bj2840725

Price R. G., 1977, Studies on the metabolism of the renal glomerular basement membrane: Turnover measurements in the rat with the use of radiolabeled amino acids, J. Biol. Chem., 252, 8597, 10.1016/S0021-9258(19)75262-4

Pupilli C., 1992, Distribution and content of renin and renin mRNA in remnant kidney of adult rat, Am. J. Physiol., 263, F731

Romen W., 1976, Synthesis of the glomerular basement membrane in the rat kidney: Autoradiographic studies with the light and electron microscope, Virchows Arch., 20, 125

Rosenzweig L. J., 1982, Removal of sulfated (heparan sulfate) or nonsulfated (hyaluronic acid) glycosaminogly‐cans results in increased permeability of the glomerular basement membrane to 125I‐bovine serum albumin, Lab. Invest., 47, 177

10.1021/bi00591a028

10.1083/jcb.111.4.1685

10.1016/0012-1606(84)90119-2

10.1083/jcb.110.3.825

10.1073/pnas.82.10.3296

Stow J. L., 1989, Basement membrane heparan sulfate proteoglycan is the main proteoglycan synthesized by glomerular epithelial cells in culture, Am. J. Pathol., 135, 637

Striker G. E., 1980, Human glomerular cells in vitro: Isolation and characterization, Transplant. Proc., 12, 88

10.1126/science.2454508

10.1111/j.1432-1033.1989.tb14673.x

10.1002/path.1711100306

Witney F. R., 1984, Highly repeated DNA families in the rat, J. Biol. Chem., 259, 10481, 10.1016/S0021-9258(18)90989-0

10.1177/34.1.3510247

Yurchenco P. D., 1987, Self‐assembly of a high molecular weight basement membrane heparan sulfate proteoglycan into dimers and oligomers, J. Biol. Chem., 262, 17668, 10.1016/S0021-9258(18)45431-2