Modulating Bone morphogenetic protein (BMP) and Transforming growth factor-beta (TGF-β) signalling with green tea catechins in mammalian cells

Familial cases of pulmonary arterial hypertension (PAH) are often caused by germline mutations, the most common being a loss of characteristic mutation in the BMPR2 gene, a member of the TGFβ Superfamily. In this study, it was hypothesised that these green tea catechin compounds might inhibit TGFβ signalling while promoting BMP signalling. This study demonstrates that these green tea catechin compounds inhibit TGFβR-II and TGFβ1-induced SMAD-dependent by reducing reporter activity, reduce the phosphorylation of SMAD3 proteins, and decrease the expression of pai-1 transcript. These green tea catechin compounds also decreased the BMP4-induced phosphorylation of p38 mitogen-activated protein kinase proteins and promoted BMP4-induced SMAD-dependent by increasing the phosphorylation of BMP4-induced SMAD1/5 protein expressions. Also, these catechin compounds increased id1 target gene expression in the presence and absence of BMP type-II-receptors. The data of this study demonstrated that catechin compounds might exert an inhibitory effect on TGFβ signalling and promote BMP signalling. Finally, in this research, elevated expression of CALM1, DYRK2, and MPP1 genes have been observed in the nucleus as revealed by their induction of pai-1 and id1-specific target gene expression, also modulating the regulation of specific ligand-induced phosphorylation of SMAD3 and SMAD1/5 proteins respectively. Therefore, CALM1, DYRK2, and MPP1 may have a nuclear function in modulating TGFβ and BMP signalling pathways respectively. These results obtained from this research have experimental and clinical potentials for identifying a novel treatment for PAH.

Grantor dc:publisher.institution

University of Bradford

Author dc:creator

• Nganwuchu, Chinyere C.

Advisors dc:contributor.advisor

• Shnyder, Steven
• Mprah Barnieh, Francis
• Anyanwagu, Uche

• Pulmonary arterial hypertension
• Bone morphogenetic protein (BMP)
• Therapeutic
• TGF-Beta signalling
• Targets
• Proliferation
• Genes
• Catechins
• Ligands
• Pulmonary arterial smooth muscle cells (PASMCs)

Statement dc:rights

• <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.

Language dc:language.iso

en

Repository record dc:identifier.uri

https://bradscholars.brad.ac.uk/handle/10454/20664

OAI identifier oai:identifier

oai:bradscholars.brad.ac.uk:10454/20664