Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/19308
Título
Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption.
Autor(es)
Zarkada, Georgia | Chen, Xun | Zhou, Xuetong | Lange, Martin | Zeng, Lei | Lv, Wenyu | Zhang, Xuan | Li, Yunhua | Zhou, Weibin | Liu, Keli | Chen, Dongying | Ricard, Nicolas | Liao, James | Kim, Young-Bum | Benedito, Rui CNIC | Claesson-Welsh, Lena | Alitalo, Kari | Simons, Michael | Ju, Rong | Li, Xuri | Eichmann, Anne | Zhang, Feng
Fecha de publicación
2023-08-04
Cita
Circ Res. 2023 Aug 4;133(4):333-349.
Idioma
Inglés
Tipo de documento
journal article
Resumen
BACKGROUND
Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell junctions between capillary lymphatic endothelial cells (LECs), whereas closed junctions in collecting LECs prevent lymph leakage. LEC junctions are known to dynamically remodel in development and disease, but how lymphatic permeability is regulated remains poorly understood.
METHODS
We used various genetically engineered mouse models in combination with cellular, biochemical, and molecular biology approaches to elucidate the signaling pathways regulating junction morphology and function in lymphatic capillaries.
RESULTS
By studying the permeability of intestinal lacteal capillaries to lipoprotein particles known as chylomicrons, we show that ROCK (Rho-associated kinase)-dependent cytoskeletal contractility is a fundamental mechanism of LEC permeability regulation. We show that chylomicron-derived lipids trigger neonatal lacteal junction opening via ROCK-dependent contraction of junction-anchored stress fibers. LEC-specific ROCK deletion abolished junction opening and plasma lipid uptake. Chylomicrons additionally inhibited VEGF (vascular endothelial growth factor)-A signaling. We show that VEGF-A antagonizes LEC junction opening via VEGFR (VEGF receptor) 2 and VEGFR3-dependent PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) activation of the small GTPase RAC1 (Rac family small GTPase 1), thereby restricting RhoA (Ras homolog family member A)/ROCK-mediated cytoskeleton contraction.
CONCLUSIONS
Our results reveal that antagonistic inputs into ROCK-dependent cytoskeleton contractions regulate the interconversion of lymphatic junctions in the intestine and in other tissues, providing a tunable mechanism to control the lymphatic barrier.
MESH
Lymphatic Vessels | Monomeric GTP-Binding Proteins | Mice | Animals | Vascular Endothelial Growth Factor A | Endothelial Cells | Phosphatidylinositol 3-Kinases | Chylomicrons | Capillary Permeability
Versión en línea
DOI
Aparece en las colecciones
Ficheros en el ítem
![Acceso Abierto Acceso Abierto](/themes/Mirage2/images/openAccess.png)
- Nombre:
- Chylomicrons Regulate Lactea_Circ ...
- Tamaño:
- 15.31Mb
- Formato:
- Descripción:
- Artículo