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Sökning: WFRF:(Benedito Rui) > Chylomicrons Regula...

Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption

Zarkada, Georgia (författare)
Yale Univ, Cardiovasc Res Ctr, Dept Cellular & Mol Physiol, Sch Med, New Haven, CT 06511 USA.;Univ Connecticut, Now Dept Physiol & Neurobiol, Storrs, CT USA.
Chen, Xun (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
Zhou, Xuetong (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
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Lange, Martin (författare)
Yale Univ, Cardiovasc Res Ctr, Dept Cellular & Mol Physiol, Sch Med, New Haven, CT 06511 USA.
Zeng, Lei (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
Lv, Wenyu (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
Zhang, Xuan (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
Li, Yunhua (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
Zhou, Weibin (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
Liu, Keli (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
Chen, Dongying (författare)
Yale Univ, Cardiovasc Res Ctr, Dept Cellular & Mol Physiol, Sch Med, New Haven, CT 06511 USA.
Ricard, Nicolas (författare)
Yale Univ, Cardiovasc Res Ctr, Dept Cellular & Mol Physiol, Sch Med, New Haven, CT 06511 USA.;Univ Grenoble Alpes, Lab Biosante U1292, INSERM, CEA, Grenoble, France.
Liao, James (författare)
Univ Arizona, Banner Univ Med Ctr, Coll Med, Tucson, AZ USA.
Kim, Young-Bum (författare)
Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA.;Harvard Med Sch, Boston, MA USA.
Benedito, Rui (författare)
Ctr Nacl Invest Cardiovasc CN, Mol Genet Angiogenesis Grp, Madrid, Spain.
Claesson-Welsh, Lena (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi
Alitalo, Kari (författare)
Univ Helsinki, Wihuri Res Inst, Biomedicum, Helsinki, Finland.;Univ Helsinki, Translat Canc Med Program, Biomedicum, Helsinki, Finland.
Simons, Michael (författare)
Yale Univ, Cardiovasc Res Ctr, Dept Cellular & Mol Physiol, Sch Med, New Haven, CT 06511 USA.
Ju, Rong (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
Li, Xuri (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.
Eichmann, Anne (författare)
Yale Univ, Cardiovasc Res Ctr, Dept Cellular & Mol Physiol, Sch Med, New Haven, CT 06511 USA.;Paris Cardiovasc Res Ctr, INSERM, U970, Paris, France.;Yale Univ, Cardiovasc Res Ctr, Sch Med, New Haven, CT 06510 USA.;Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA.
Zhang, Feng (författare)
Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China.;Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou 510060, Peoples R China.
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Yale Univ, Cardiovasc Res Ctr, Dept Cellular & Mol Physiol, Sch Med, New Haven, CT 06511 USA;Univ Connecticut, Now Dept Physiol & Neurobiol, Storrs, CT USA. Sun Yat sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou, Peoples R China. (creator_code:org_t)
Lippincott Williams & Wilkins, 2023
2023
Engelska.
Ingår i: Circulation Research. - : Lippincott Williams & Wilkins. - 0009-7330 .- 1524-4571. ; 133:4, s. 333-349
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

chylomicrons
endothelial cells
lipid
permeability
vascular endothelial growth factor A

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