Heartiest congratulations to GNOBB member Dr. Talat Nasim and his team at the University of Bradford, UK. for their recent publication in the prestigious journal "Trends in Pharmacological Sciences" (Impact Factor 13.5). The article entitled Targeting the TGF-β signaling pathway for resolution of pulmonary arterial hypertension is now available online in Trends in Pharmacological Sciences. Dr. Talat Nasim shared the following personalized URL with GNOBB members providing 50 days' free access to the article which can be downloaded free of cost till June 25, 2021
Pulmonary Arterial Hypertension (PAH) is a life-threatening condition that is caused by narrowing of the arteries that supply blood to the lungs which ultimately leads to heart failure. This narrowing can be caused by sustainable elevation of Pulmonary artery pressure (PAP). Current therapies for PAH are very costly. It has been observed that heterozygous germline mutations in the BMPRII receptor causes >80% of the heritable and familial cases of PAH. BMPR2 mutations perturb the balance between bone morphogenetic protein (BMP) and TGF-β pathways. Mutations in the genes of this signaling pathway can ultimately lead to loss of the growth-suppressive effect of BMP on vascular cells. This also enhances resistance to cell death (apoptosis) and excessive proliferation in pulmonary artery smooth muscle cells. (PASSCMC) that are deficient in the BMPRII receptor. Thus it can contribute to the narrowing of the pulmonary vascular lumen.
BMPRII deficiency leads to an abnormal overactivation of the TGF-β1 signaling pathway. The team proposed BMP signaling as a therapeutic target. It was observed that agents which promote BMPRII-mediated signaling, inhibit the overactive TGF-βsignaling. So balancing these two signaling pathways may provide protection from PAH. They concluded that regulating either TGF-β or BMP signaling may be effective in reversing or preventing PAH progression and a combinational therapy that elicits anti-TGF-β and proBMP activities might be more effective.
This research, led by Dr. Talat Nasim, is a team effort of Translational Medicine Laboratory at the University of Bradford, Bradford, Department of Pharmaceutical Technology at the University of Dhaka, and the Centre for Health, Agriculture, and Socio-economic Advancements (CHASA) at Lalmonirhat, Bangladesh.