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.

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 degreesC), cells produced only MMP2. Shifting cells to a nonpermissive temperature (39.5 degreesC) 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 degreesC 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.