AIMS: The study set out to investigate whether the osteopontin (OPN)-CD44-integrin-receptor-system is differently regulated during nephrogenesis in inborn nephron deficit, a major determinant of human primary hypertension and cardiovascular disease in adult life. METHODS: We compared a genetic rat model with an inherited nephron deficit, the Munich-Wistar-Froemter rat (MWF), to normotensive Wistar rats during nephrogenesis at day 19 of fetal development (E19) and at postpartal day 7 (D7). RESULTS: Renal OPN mRNA (-75%, P<0.05) and protein expression (-38%, P<0.05) were strongly decreased at E19 in MWF compared to Wistar. Renal mRNA-expression of CD44 was increased at E19 in MWF (+271%, P<0.05). At D7, renal OPN protein expression was increased (+115%, P<0.05) and renal mRNA-expression of CD44 remained elevated compared to Wistar control (+127%, P<0.05). CONCLUSIONS: Altered fetal expression of the OPN-CD44-integrin-receptor-system in the MWF model points to a possible role in low nephron number hypertension and cardiovascular disease.
AIMS: The study set out to investigate whether the osteopontin (OPN)-CD44-integrin-receptor-system is differently regulated during nephrogenesis in inborn nephron deficit, a major determinant of human primary hypertension and cardiovascular disease in adult life. METHODS: We compared a genetic rat model with an inherited nephron deficit, the Munich-Wistar-Froemter rat (MWF), to normotensive Wistar rats during nephrogenesis at day 19 of fetal development (E19) and at postpartal day 7 (D7). RESULTS:Renal OPN mRNA (-75%, P<0.05) and protein expression (-38%, P<0.05) were strongly decreased at E19 in MWF compared to Wistar. Renal mRNA-expression of CD44 was increased at E19 in MWF (+271%, P<0.05). At D7, renal OPN protein expression was increased (+115%, P<0.05) and renal mRNA-expression of CD44 remained elevated compared to Wistar control (+127%, P<0.05). CONCLUSIONS: Altered fetal expression of the OPN-CD44-integrin-receptor-system in the MWF model points to a possible role in low nephron number hypertension and cardiovascular disease.
Authors: Edwin J Baldelomar; Jennifer R Charlton; Scott C Beeman; Bradley D Hann; Luise Cullen-McEwen; Valeria M Pearl; John F Bertram; Teresa Wu; Min Zhang; Kevin M Bennett Journal: Kidney Int Date: 2016-02 Impact factor: 10.612