Pathological lymphangiogenesis is modulated by galectin-8-dependent crosstalk between podoplanin and integrin-associated VEGFR-3
(2016) In Nature Communications 7.- Abstract
Lymphangiogenesis plays a pivotal role in diverse pathological conditions. Here, we demonstrate that a carbohydrate-binding protein, galectin-8, promotes pathological lymphangiogenesis. Galectin-8 is markedly upregulated in inflamed human and mouse corneas, and galectin-8 inhibitors reduce inflammatory lymphangiogenesis. In the mouse model of corneal allogeneic transplantation, galectin-8-induced lymphangiogenesis is associated with an increased rate of corneal graft rejection. Further, in the murine model of herpes simplex virus keratitis, corneal pathology and lymphangiogenesis are ameliorated in Lgals8 -/- mice. Mechanistically, VEGF-C-induced lymphangiogenesis is significantly reduced in the Lgals8 -/- and Pdpn... (More)
Lymphangiogenesis plays a pivotal role in diverse pathological conditions. Here, we demonstrate that a carbohydrate-binding protein, galectin-8, promotes pathological lymphangiogenesis. Galectin-8 is markedly upregulated in inflamed human and mouse corneas, and galectin-8 inhibitors reduce inflammatory lymphangiogenesis. In the mouse model of corneal allogeneic transplantation, galectin-8-induced lymphangiogenesis is associated with an increased rate of corneal graft rejection. Further, in the murine model of herpes simplex virus keratitis, corneal pathology and lymphangiogenesis are ameliorated in Lgals8 -/- mice. Mechanistically, VEGF-C-induced lymphangiogenesis is significantly reduced in the Lgals8 -/- and Pdpn -/- mice; likewise, galectin-8-induced lymphangiogenesis is reduced in Pdpn -/- mice. Interestingly, knockdown of VEGFR-3 does not affect galectin-8-mediated lymphatic endothelial cell (LEC) sprouting. Instead, inhibiting integrins α1β1 and α5β1 curtails both galectin-8- and VEGF-C-mediated LEC sprouting. Together, this study uncovers a unique molecular mechanism of lymphangiogenesis in which galectin-8-dependent crosstalk among VEGF-C, podoplanin and integrin pathways plays a key role.
(Less)
- author
- organization
- publishing date
- 2016-04-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 7
- article number
- 11302
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:84964319308
- pmid:27066737
- wos:000373832000001
- ISSN
- 2041-1723
- DOI
- 10.1038/ncomms11302
- language
- English
- LU publication?
- yes
- id
- b25ed55f-e79f-4605-9903-47b6c9013158
- date added to LUP
- 2016-10-03 09:55:07
- date last changed
- 2024-08-09 19:44:15
@article{b25ed55f-e79f-4605-9903-47b6c9013158, abstract = {{<p>Lymphangiogenesis plays a pivotal role in diverse pathological conditions. Here, we demonstrate that a carbohydrate-binding protein, galectin-8, promotes pathological lymphangiogenesis. Galectin-8 is markedly upregulated in inflamed human and mouse corneas, and galectin-8 inhibitors reduce inflammatory lymphangiogenesis. In the mouse model of corneal allogeneic transplantation, galectin-8-induced lymphangiogenesis is associated with an increased rate of corneal graft rejection. Further, in the murine model of herpes simplex virus keratitis, corneal pathology and lymphangiogenesis are ameliorated in Lgals8 -/- mice. Mechanistically, VEGF-C-induced lymphangiogenesis is significantly reduced in the Lgals8 <sup>-/-</sup> and Pdpn <sup>-/-</sup> mice; likewise, galectin-8-induced lymphangiogenesis is reduced in Pdpn <sup>-/-</sup> mice. Interestingly, knockdown of VEGFR-3 does not affect galectin-8-mediated lymphatic endothelial cell (LEC) sprouting. Instead, inhibiting integrins α1β1 and α5β1 curtails both galectin-8- and VEGF-C-mediated LEC sprouting. Together, this study uncovers a unique molecular mechanism of lymphangiogenesis in which galectin-8-dependent crosstalk among VEGF-C, podoplanin and integrin pathways plays a key role.</p>}}, author = {{Chen, Wei Sheng and Cao, Zhiyi and Sugaya, Satoshi and Lopez, Maria J. and Sendra, Victor G. and Laver, Nora and Leffler, Hakon and Nilsson, Ulf J. and Fu, Jianxin and Song, Jianhua and Xia, Lijun and Hamrah, Pedram and Panjwani, Noorjahan}}, issn = {{2041-1723}}, language = {{eng}}, month = {{04}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{Pathological lymphangiogenesis is modulated by galectin-8-dependent crosstalk between podoplanin and integrin-associated VEGFR-3}}, url = {{http://dx.doi.org/10.1038/ncomms11302}}, doi = {{10.1038/ncomms11302}}, volume = {{7}}, year = {{2016}}, }