Matrix Metalloproteinase 2 (MMP2) and MMP9 Are Produced by Kidney Collecting Duct Principal Cells but Are Differentially Regulated by SV40 Large-T, Arginine Vasopressin, and Epidermal Growth Factor*
- From the ‡INSERM, Unité 489, Hôpital Tenon, 75020 Paris, France and the ¶School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom
Abstract
We analyzed the expression and regulation of matrix metalloproteinase 2 (MMP2) and MMP9 gelatinases in a rabbit kidney collecting duct principal cell line (RC.SVtsA58) (Prié, D., Ronco, P. M., Baudouin, B., Géniteau-Legendre, M., Antoine, M., Piedagnel, R., Estrade, S., Lelongt, B., Verroust, P. J., Cassingéna, R., and Vandewalle, A. (1991) J. Cell Biol. 113, 951–962) infected with the temperature-sensitive (ts) SV40 strain tsA58. At the permissive temperature (33 °C), cells produced only MMP2. Shifting cells to a nonpermissive temperature (39.5 °C) induced a marked increase in total gelatinolytic activity due to an increase of MMP2 and an induction of MMP9 synthesis. This effect was attributed to large-T inactivation at 39.5 °C because it was abolished by re-infecting the cells with wild-type SV40 strain LP. Run-on experiments showed that negative regulation of MMP2 and MMP9 by large-T was transcriptional and posttranscriptional, respectively. MMP2 and MMP9 were also produced by primary cultures of collecting duct cells. In rabbit kidney, both MMP2 and MMP9 were almost exclusively expressed in collecting duct cells, where an unexpected apical localization was observed. Arginine vasopressin and epidermal growth factor, which exert opposite hydroosmotic effects in the collecting duct, also exhibited contrasted effects on MMP9 synthesis. Epidermal growth factor increased but arginine vasopressin suppressed MMP9 at a posttranscriptional level, whereas MMP2 was not affected. These results suggest a specific physiological role of MMP2 and MMP9 in principal cells of renal collecting duct.
Footnotes
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↵* This work was supported by INSERM, the Association pour la Recherche sur le Cancer, and the Arthritis and Rheumatism Campaign, United Kingdom.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.
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↵§ To whom correspondence should be addressed. Tel.: 33-1-56-01-65-12; Fax: 33-1-56-01-62-17. E-mail:remi.piedagnel{at}tnn.ap-hop-paris.fr.
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↵2 M. L. Cittanova, unpublished results.
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↵3 F. Le Goas and R. Piedagnel, unpublished results.
- Abbreviations:
- MMP
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matrix metalloproteinase
- APMA
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p-aminophenyl mercuric acetate
- AVP
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arginine vasopressin
- ECM
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extracellular matrix
- EGF
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epidermal growth factor
- GAPDH
-
glyceraldehyde phosphodehydrogenase
- TIMP
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tissue inhibitor of matrix metalloprotainase
- ts
-
temperature-sensitive
- PBS
-
phosphate-buffered saline
- AP-2
-
activator protein-2.
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- Received July 27, 1998.
- Revision received October 23, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
