GAL3 Excretion Regulates Smooth Muscle Cell Survival and Proliferation

• Published in: The FASEB journal 2022-05, Vol.36 (S1), p.n/a
• Main Authors: Haigh, Stephen, Li, Xi, Bordan, Zsuzsanna, Sellers, Hunter, Meadows, Mary Louise, Barman, Scott, Fulton, David
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2022.36.S1.L7886

Pulmonary arterial hypertension (PAH) is a complex and fatal disorder characterized by an unrelenting increase in pulmonary arterial pressure. Excessive proliferation of pulmonary artery smooth muscle cells (PASMC) leads to increased vascular resistance and eventually right ventricular failure and death. Our laboratory has identified a key role for Galectin‐3 (GAL‐3) in PAH. However, the mechanisms by which GAL‐3 alters PASMC behavior remains poorly understood. GAL‐3 contains a functional BH1 like domain that has an NWGR sequence with high homology to the anti‐apoptotic protein, BCL2, and this domain has previously been shown to be functional in cancer cell lines. Our hypothesis is GAL‐3 upregulation plays an important role in driving PASMC proliferation through repression of apoptosis via this NWGR domain. Using adenoviral vector encoding the GAL‐3 G182A mutation and isolated GAL‐3 PASMCs from a GAL3 KO rat (RPASMC). Our in vitro studies show that overexpression of GAL‐3 G182A causes a decrease in viability upon treatment overnight with 0.5% serum containing media(p