Long non-coding RNA LASSIE regulates shear stress sensing and endothelial barrier function

Area of Science:

• Vascular Biology
• Molecular Biology
• Biophysics

Background:

• Blood vessels experience shear stress from blood flow, impacting vascular homeostasis.
• Adherens junctions (AJs) are key regulators of endothelial barrier function and shear stress response.
• Endothelial cell-cell contacts and alignment are critical for maintaining blood vessel integrity.

Purpose of the Study:

• To investigate the role of long non-coding RNAs in endothelial shear stress response.
• To identify novel regulators of adherens junction stability under mechanical forces.
• To elucidate the molecular mechanisms by which LASSIE influences endothelial cell behavior.

Main Methods:

• RNA affinity purification to identify LASSIE-interacting proteins.
• Endothelial cell culture and manipulation (e.g., LASSIE silencing).
• Immunofluorescence microscopy and biochemical assays to assess cell junctions and cytoskeletal interactions.

Main Results:

• LASSIE (linc00520) is induced by shear stress and stabilizes adherens junctions in endothelial cells.
• LASSIE silencing impairs endothelial cell survival, cell-cell contacts, and alignment.
• LASSIE directly interacts with junctional proteins (e.g., PECAM-1) and nestin, linking AJs to the microtubule cytoskeleton via VE-cadherin.

Conclusions:

• LASSIE is a critical mediator of endothelial response to shear stress.
• LASSIE connects adherens junctions to the cytoskeleton through the nestin-VE-cadherin complex.
• LASSIE plays a vital role in maintaining vascular barrier function and integrity.