Jan Danser

Professor in Pharmacology @ErasmusMC

[Jan Danser @JanDanser]

@Carmendemigue12 @HyperAHA Thank you all for your great questions! Yuan and Jan #HYPHIP

[Jan Danser @JanDanser]

@NakagawaPablo @HyperAHA Thank you all for these great questions! Yuan and Jan

[Jan Danser @JanDanser]

@NakagawaPablo @HyperAHA @JavierGomez_PhD Q22 The intracellular occurrence of angiotensin II depends on AT1 receptor-mediated internalization, and we have never been able to demonstrate intracellular angiotensin generation. #HYPHIP

[Jan Danser @JanDanser]

@Carmendemigue12 @HyperAHA Answering this would require crystallographic knowledge, making use of highly purified prorenin and megalin... We are currently unable to do this ourselves. #HYPHIP

[Jan Danser @JanDanser]

@NakagawaPablo @mari_br_montrea @HyperAHA Yes, we fully agree, and this is our next goal! #HYPHIP

[Jan Danser @JanDanser]

@NakagawaPablo @HyperAHA Q Pablo on PRR We observed prorenin activation following its internalization. The latter depended on the PRR, but whether the former also is PRR-mediated we do not know yet. #HYPHIP

[Jan Danser @JanDanser]

@Carmendemigue12 @HyperAHA Q20 Previous data from our group have demonstrated that the M6P receptor is a clearance receptor, in multiple cells, and probably also in ciPTEC. #HYPHIP

[Jan Danser @JanDanser]

@NakagawaPablo @mari_br_montrea @HyperAHA Q Pablo Exactly, indeed albumin is competing with prorenin, and if high enough will even block prorenin uptake! #HYPHIP

[Jan Danser @JanDanser]

@guto_montezano @YuanSun33698043 @NakagawaPablo @fjorios @HyperAHA Q16 Guto This would be very exciting, but we are not aware of any data on this so far! #HYPHIP

[Jan Danser @JanDanser]

@DrDudenbostel @NakagawaPablo Q16 Tanja E.g., Ang II, pH, hyperglycemia, etc.

[Jan Danser @JanDanser]

@Carmendemigue12 @guto_montezano @NakagawaPablo @HyperAHA Q Carmen Yes, this is possible, but the net effect is the same: less reabsorption! #HYPHIP

[Jan Danser @JanDanser]

@mari_br_montrea @guto_montezano @NakagawaPablo @HyperAHA Yes, this is one of our current research topics, since (pro)renin levels in urine of preeclamptic women are very high! #HYPHIP

[Jan Danser @JanDanser]

@NakagawaPablo @HyperAHA @JavierGomez_PhD @pinacate10 Thank you for letting us know! #HYPHIP

[Jan Danser @JanDanser]

@NakagawaPablo @HyperAHA Q14 Yes. In fact, we observed prorenin degradation after loading the cells with prorenin. This was unrelated to megalin. Binding to a renin inhibitor blocked degradation because this stabilizes the molecule. We did not use proteasome inhibitors. #HYPHIP

[Jan Danser @JanDanser]

@Carmendemigue12 @HyperAHA Q13 Yes, there are many (currently >40 known), and among them is angiotensinogen. #HYPHIP

[Jan Danser @JanDanser]

@NakagawaPablo @Carmendemigue12 @HyperAHA Yes, for instance in placental trophoblasts... #HYPHIP

[Jan Danser @JanDanser]

@mari_br_montrea @NakagawaPablo @HyperAHA Q Mariane We would love to do this, but haven't so far! #HYPHIP