VEGF-D-mediated signaling in tendon cells is involved in degenerative processes.
Achilles Tendon
/ metabolism
Animals
Cell Movement
/ physiology
Cell Proliferation
/ physiology
Extracellular Matrix
/ metabolism
Female
Humans
Male
Mice
Neovascularization, Pathologic
/ metabolism
RNA, Messenger
/ metabolism
Rats
Rats, Inbred Lew
Rats, Sprague-Dawley
Receptors, Vascular Endothelial Growth Factor
/ metabolism
Signal Transduction
/ physiology
Vascular Endothelial Growth Factor D
/ metabolism
VEGF signaling
biomechanics
bioreactor
extracellular matrix degradation
fibrosis
tendon cells
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
14
12
2021
received:
17
05
2021
accepted:
14
12
2021
entrez:
19
1
2022
pubmed:
20
1
2022
medline:
15
2
2022
Statut:
ppublish
Résumé
Vascular endothelial growth factor (VEGF) signaling is crucial for a large variety of cellular processes, not only related to angiogenesis but also in nonvascular cell types. We have previously shown that controlling angiogenesis by reducing VEGF-A signaling positively affects tendon healing. We now hypothesize that VEGF signaling in non-endothelial cells may contribute to tendon pathologies. By immunohistochemistry we show that VEGFR1, VEGFR2, and VEGFR3 are expressed in murine and human tendon cells in vivo. In a rat Achilles tendon defect model we show that VEGFR1, VEGFR3, and VEGF-D expression are increased after injury. On cultured rat tendon cells we show that VEGF-D stimulates cell proliferation in a dose-dependent manner; the specific VEGFR3 inhibitor SAR131675 reduces cell proliferation and cell migration. Furthermore, activation of VEGFR2 and -3 in tendon-derived cells affects the expression of mRNAs encoding extracellular matrix and matrix remodeling proteins. Using explant model systems, we provide evidence, that VEGFR3 inhibition prevents biomechanical deterioration in rat tail tendon fascicles cultured without load and attenuates matrix damage if exposed to dynamic overload in a bioreactor system. Together, these results suggest a strong role of tendon cell VEGF signaling in mediation of degenerative processes. These findings give novel insight into tendon cell biology and may pave the way for novel treatment options for degenerative tendon diseases.
Identifiants
pubmed: 35044682
doi: 10.1096/fj.202100773RRR
doi:
Substances chimiques
RNA, Messenger
0
VEGFD protein, human
0
Vascular Endothelial Growth Factor D
0
Receptors, Vascular Endothelial Growth Factor
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22126Informations de copyright
© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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