Preprint Article Version 1 This version is not peer-reviewed

Effects of Modulating BMP9, BMPR2, and AQP1 on Bmp-Signaling in Human Pulmonary Microvascular Endothelial Cells

Version 1 : Received: 28 June 2024 / Approved: 1 July 2024 / Online: 1 July 2024 (09:21:33 CEST)

How to cite: Lotsios, N. S.; Keskinidou, C.; Dimopoulou, I.; Kotanidou, A.; Langleben, D.; Orfanos, S. E.; Vassiliou, A. G. Effects of Modulating BMP9, BMPR2, and AQP1 on Bmp-Signaling in Human Pulmonary Microvascular Endothelial Cells. Preprints 2024, 2024070057. https://doi.org/10.20944/preprints202407.0057.v1 Lotsios, N. S.; Keskinidou, C.; Dimopoulou, I.; Kotanidou, A.; Langleben, D.; Orfanos, S. E.; Vassiliou, A. G. Effects of Modulating BMP9, BMPR2, and AQP1 on Bmp-Signaling in Human Pulmonary Microvascular Endothelial Cells. Preprints 2024, 2024070057. https://doi.org/10.20944/preprints202407.0057.v1

Abstract

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive in-crease in mean pulmonary arterial pressure. Mutations in the BMPR2 and AQP1 genes have been described in familial PAH. The bone morphogenetic proteins BMP9 and BMP10 bind with high affinity to BMPR2. Administration of BMP9 has been proposed as a potential therapeutic strategy against PAH, although recent conflicting evidence dispute the effect of such practice. Considering the involvement of the above molecules in PAH onset, progression, and therapeutic value, we ex-amined the effects of modulation of BMP9, BMPR2, and AQP1 on BMP9, BMP10, BMPR2, AQP1, and TGFB1 expression in human pulmonary microvascular endothelial cells in vitro. Our results demonstrated that silencing the BMPR2 gene resulted in increased expression of its two main ligands, namely BMP9 and BMP10. Exogenous administration of BMP9 caused return of BMP10 to basal levels, while restored the decreased AQP1 protein levels and the decreased TGFB1 mRNA and protein expression levels caused by BMPR2 silencing. Moreover, AQP1 gene silencing also resulted in increased expression of BMP9 and BMP10. Our results might possibly imply that the effect of exogenously administered BMP9 on molecules participating in the BMP-signaling pathway could depend on the expression levels of BMPR2. Taken together, these results may pro-vide insight into the highly complex interactions of the BMP-signaling pathway.

Keywords

PAH; BMP9; BMPR2; AQP1

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.