Proliferating and Migrating Mesangial Cells Responding to Injury Express a Novel Receptor Protein-tyrosine Phosphatase in Experimental Mesangial Proliferative Glomerulonephritis*
- Matthew B. Wright‡§,
- Christian Hugo¶‖,
- Ronald Seifert‡,
- Christine M. Disteche‡ and
- Daniel F. Bowen-Pope‡**
- From the ‡Department of Pathology and the¶Division of Nephrology, University of Washington, Seattle, Washington 98105-7470
Abstract
The mesangial cell provides structural support to the kidney glomerulus. A polymerase chain reaction-based cDNA display approach identified a novel protein-tyrosine phosphatase, rPTP-GMC1, whose transcript expression is transiently and dramatically up-regulated during the period of mesangial cell migration and proliferation that follows mesangial cell injury in the anti-Thy 1 model of mesangial proliferative glomerulonephritis in the rat.In situ hybridization analysis confirmed that rPTP-GMC1 mRNA is up-regulated specifically by mesangial cells responding to the injury and is not detectable in other cells in the kidney or in many normal tissues. In cell culture, rPTP-GMC1 is expressed by mesangial cells but not by glomerular endothelial or epithelial cells (podocytes). The longest transcript (7.5 kilobases) encodes a receptor-like protein-tyrosine phosphatase consisting of a single catalytic domain, a transmembrane segment, and 18 fibronectin type III-like repeats in the extracellular segment. A splice variant predicts a truncated molecule missing the catalytic domain. rPTP-GMC1 maps to human chromosome 12q15 and to the distal end of mouse chromosome 10. The predicted structure of rPTP-GMC1 and its pattern of expression in vivo and in culture suggest that it plays a role in regulating the adhesion and migration of mesangial cells in response to injury.
Footnotes
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↵* This work was supported by a grant from F. Hoffmann La-Roche, Basel, Switzerland for cardiovascular research (D.F.B.-P.) and by grants from the National Institutes of Health (C.M.D.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF063249, AF073998, and AF073999.
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↵§ Current address: Dept. of Cardiovascular Research, F. Hoffmann-La Roche, 4070 Basel, Switzerland.
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↵‖ Current address: Universität Erlangen-Nürnberg, Erlangen 91054, Germany.
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↵** To whom correspondence should be addressed: Dept. of Pathology, University of Washington, Box 357470, Seattle, WA 98195-7470. Tel.: 206-685-2148; Fax: 206-543-3644; E-mail: bp{at}u.washington.edu.
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↵2 The raw data are available on the World Wide Web (http://www.jax.org/resources/documents/cmdata).
- Abbreviations:
- PTPase
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protein-tyrosine phosphatase
- PCR
-
polymerase chain reaction
- RACE
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rapid amplification of cDNA ends
- FN-III
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fibronectin type III-like repeat
- FISH
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fluorescence in situ hybridization
- FA
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focal adhesion
- bp
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base pair(s)
- kb
-
kilobase pair(s)
- RT
-
reverse transcriptase
- MOPS
-
4-morpholinepropanesulfonic acid.
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- Received May 8, 1998.
- Revision received June 19, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
