PhD Scientific Days 2023

Molecular Sciences IV.

CCBE1 Regulates the Development and Prevents the Age-dependent Degradation of Meningeal Lymphatics

Előadó neve

Dr. Ocskay, Zsombor

Neptun code

sg1i9s

Előadó munkahelye

Department of Physiology – Semmelweis University

Előadó telefonszáma

0036205802280

Előadó e-mail címe

ocskay.zsombor@med.semmelweis-univ.hu

Az előadás címe

CCBE1 Regulates the Development and Prevents the Age-dependent Degradation of Meningeal Lymphatics

Szerző(k) neve és munkahelye

Zsombor Ocskay1, László Bálint1, Carolin Christ1, Mark L. Kahn2 and Zoltán Jakus1

1Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
2Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Bemutatás módja

Szóbeli

Szekció

Molecular Sciences IV.

Language of the presentation

English

Preferred session

Molecular Sciences

Összefoglaló szövege

Understanding organ-specific lymphatic development and function is of great importance, including the role of meningeal lymphatics. These structures develop postnatally and are altered by aging. VEGFC/VEGFR3 signaling has been shown to play an essential role in the development and maintenance of meningeal lymphatics. Recent in vitro cell line experiments and in vivo studies in zebrafish and mouse skin suggest that the collagen- and calcium-binding EGF domains 1 (CCBE1) is involved in the processing of VEGFC. However, the organ-specific role of CCBE1 in lymphangiogenesis and maintenance of lymphatics remains unclear. Here, we aimed to investigate the organ-specific functions of CCBE1 in developmental lymphangiogenesis and maintenance of meningeal lymphatics during aging. Lymphatic endothelial cell-specific immunostainings were used to characterize the meningeal lymphatic structures in wild-type and CCBE1 deficient mice at different ages, including young and old animals. The lymphatic function was monitored by injecting labeled macromolecules into the CNS, then assessing uptake and drainage to the cervical lymph nodes. We demonstrated that the inducible deletion of CCBE1 leads to impaired postnatal development of the meningeal lymphatics and decreased macromolecule drainage to deep cervical lymph nodes. The structural integrity and density of meningeal lymphatics gradually altered during aging. Furthermore, the meningeal lymphatic structures in adults showed regression after CCBE1 deletion. Collectively, our results indicate the importance of CCBE1-dependent mechanisms not only in the development, but also in the prevention of the age-related degradation of meningeal lymphatics. Therefore, targeting CCBE1 might be a good therapeutic strategy to prevent age-related degradation of meningeal lymphatics.

This work was supported by the National Research, Development and Innovation Office (K139165, TKP2021-EGA-29, TKP2021-EGA-24, NVKP_16-1-2016-0039), the European Union and the Hungarian Government (VEKOP-2.3.2-16-2016-00002, VEKOP-2.3.3-15-2016-00006).

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine

Supervisor

Dr. Zoltan Jakus

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4805

Start

15:45

End

16:00

Authors (legacy)

Zsombor Ocskay1, László Bálint1, Carolin Christ1, Mark L. Kahn2 and Zoltán Jakus1

1Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
2Cardiovascular Institute, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania