Hypoxia-induced TIMAP upregulation in endothelial cells and TIMAP-dependent tumor angiogenesis.

TGFβ-inhibited membrane associated protein (TIMAP), the endothelial cell-predominant protein phosphatase 1β regulatory subunit also known as PPP1R16B, promotes in vitro endothelial cell proliferation and angiogenic sprouting. TIMAP was first identified as a target of TGF-β1-mediated repression, but the molecular pathways regulating its expression in endothelial cells are not well-defined. This study examined the role of bone morphogenetic factor 9 (BMP9), hypoxia, and angiogenic growth factors in the regulation of TIMAP expression and determined whether TIMAP plays a role in tumor angiogenesis and growth in vivo.

Advancing Discovery Research in Nephrology in Canada: A Conference Report From the 2021 Molecules and Mechanisms Mediating Kidney Health and Disease (M3K) Scientific Meeting and Investigator Summit.

Purpose Of Conference: New discoveries arising from investigations into fundamental aspects of kidney development and function in health and disease are critical to advancing kidney care. Scientific meetings focused specifically on fundamental biology of the kidney can facilitate interactions, support the development of collaborative groups, and accelerate translation of key findings. The Canadian fundamental kidney researcher community has lacked such a forum.

The Glomerular Endothelium Restricts Albumin Filtration.

Inflammatory activation and/or dysfunction of the glomerular endothelium triggers proteinuria in many systemic and localized vascular disorders. Among them are the thrombotic microangiopathies, many forms of glomerulonephritis, and acute inflammatory episodes like sepsis and COVID-19 illness. Another example is the chronic endothelial dysfunction that develops in cardiovascular disease and in metabolic disorders like diabetes.

TIMAP inhibits endothelial myosin light chain phosphatase by competing with MYPT1 for the catalytic protein phosphatase 1 subunit PP1cβ.

Transforming growth factor-β membrane associated protein (TIMAP) is an endothelial cell (EC)-predominant PP1 regulatory subunit and a member of the myosin phosphatase target (MYPT) protein family. The MYPTs preferentially bind the catalytic protein phosphatase 1 subunit PP1cβ, forming myosin phosphatase holoenzymes. We investigated whether TIMAP/PP1cβ could also function as a myosin phosphatase.