Thrombospondin-1 induction and VEGF reduction by proteasome inhibition
The present study focuses on investigating the expression of thrombospondin-1 (TSP-1), a natural inhibitor of neovascularization. Immunofluorescent staining was used to detect the expression of TSP-1 in rabbit corneal tissue with vascularization induced by limbectomy. TSP-1 was detected in healthy a...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-02-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023006047 |
| _version_ | 1811161783054893056 |
|---|---|
| author | Fawzia Bardag-Gorce Carter Hoffman Imara Meepe Monica Ferrini Richard H. Hoft Joan Oliva Yutaka Niihara |
| author_facet | Fawzia Bardag-Gorce Carter Hoffman Imara Meepe Monica Ferrini Richard H. Hoft Joan Oliva Yutaka Niihara |
| author_sort | Fawzia Bardag-Gorce |
| collection | DOAJ |
| description | The present study focuses on investigating the expression of thrombospondin-1 (TSP-1), a natural inhibitor of neovascularization. Immunofluorescent staining was used to detect the expression of TSP-1 in rabbit corneal tissue with vascularization induced by limbectomy. TSP-1 was detected in healthy and Cultured Autologous Oral Mucosal Epithelial Cell Sheet (CAOMECS) grafted rabbit corneas. TSP-1 was not detected in diseased corneas. Rabbit and human primary oral mucosal and corneal epithelial cells were cultured and treated with proteasome inhibitor (PI) in vitro. Changes in the expression of TSP-1, HIF-1 alpha and 2 alpha, VEGF-A, and VEGF receptor were analyzed by Western blotting. Neovascularization developed in rabbits’ corneas as early as 1 month after limbectomy and was stable for at least 3 months. HIF-1 alpha and VEGF-A expression was reduced in CAOMECS grafted corneas, as compared to sham corneas. While TSP-1 expression was decreased in injured corneas, it was expressed in CAOMECS grafted corneas, but still less expressed compared to healthy corneas. PI treatment, of human oral mucosal and corneal epithelial cells increased TSP-1 expression and reduced VEGF-A expression. The results showed that TSP-1 expression was lost in injured corneal surface and that CAOMECS grafting restored TSP-1 expression to certain extent. Proteasome inhibition treatment increased TSP-1 and decreased VEGF-A expression in human oral mucosal and corneal epithelial cells. The result suggests that corneal neovascularization could be managed with the inhibition of the proteasome after CAOMECS grafting and increase corneal transparency. |
| first_indexed | 2024-04-10T06:19:50Z |
| format | Article |
| id | doaj.art-b648bda6b58541deb9c03b036d1fc948 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-10T06:19:50Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-b648bda6b58541deb9c03b036d1fc9482023-03-02T05:01:23ZengElsevierHeliyon2405-84402023-02-0192e13397Thrombospondin-1 induction and VEGF reduction by proteasome inhibitionFawzia Bardag-Gorce0Carter Hoffman1Imara Meepe2Monica Ferrini3Richard H. Hoft4Joan Oliva5Yutaka Niihara6The Lundquist Institute at Harbor UCLA Medical Center, Torrance, CA, 90502, USA; Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA; Corresponding author. The Lundquist Institute at Harbor UCLA Medical Center, Torrance, CA, 90502, USA.The Lundquist Institute at Harbor UCLA Medical Center, Torrance, CA, 90502, USA; Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USAThe Lundquist Institute at Harbor UCLA Medical Center, Torrance, CA, 90502, USACharles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USAThe Lundquist Institute at Harbor UCLA Medical Center, Torrance, CA, 90502, USAEmmaus Medical, 21250 Hawthorne Blvd, Suite 800, Torrance, CA, 90505, USAThe Lundquist Institute at Harbor UCLA Medical Center, Torrance, CA, 90502, USA; Emmaus Medical, 21250 Hawthorne Blvd, Suite 800, Torrance, CA, 90505, USAThe present study focuses on investigating the expression of thrombospondin-1 (TSP-1), a natural inhibitor of neovascularization. Immunofluorescent staining was used to detect the expression of TSP-1 in rabbit corneal tissue with vascularization induced by limbectomy. TSP-1 was detected in healthy and Cultured Autologous Oral Mucosal Epithelial Cell Sheet (CAOMECS) grafted rabbit corneas. TSP-1 was not detected in diseased corneas. Rabbit and human primary oral mucosal and corneal epithelial cells were cultured and treated with proteasome inhibitor (PI) in vitro. Changes in the expression of TSP-1, HIF-1 alpha and 2 alpha, VEGF-A, and VEGF receptor were analyzed by Western blotting. Neovascularization developed in rabbits’ corneas as early as 1 month after limbectomy and was stable for at least 3 months. HIF-1 alpha and VEGF-A expression was reduced in CAOMECS grafted corneas, as compared to sham corneas. While TSP-1 expression was decreased in injured corneas, it was expressed in CAOMECS grafted corneas, but still less expressed compared to healthy corneas. PI treatment, of human oral mucosal and corneal epithelial cells increased TSP-1 expression and reduced VEGF-A expression. The results showed that TSP-1 expression was lost in injured corneal surface and that CAOMECS grafting restored TSP-1 expression to certain extent. Proteasome inhibition treatment increased TSP-1 and decreased VEGF-A expression in human oral mucosal and corneal epithelial cells. The result suggests that corneal neovascularization could be managed with the inhibition of the proteasome after CAOMECS grafting and increase corneal transparency.http://www.sciencedirect.com/science/article/pii/S2405844023006047Corneal vascularizationProteasome inhibitionThrombospondin-1VEGF |
| spellingShingle | Fawzia Bardag-Gorce Carter Hoffman Imara Meepe Monica Ferrini Richard H. Hoft Joan Oliva Yutaka Niihara Thrombospondin-1 induction and VEGF reduction by proteasome inhibition Heliyon Corneal vascularization Proteasome inhibition Thrombospondin-1 VEGF |
| title | Thrombospondin-1 induction and VEGF reduction by proteasome inhibition |
| title_full | Thrombospondin-1 induction and VEGF reduction by proteasome inhibition |
| title_fullStr | Thrombospondin-1 induction and VEGF reduction by proteasome inhibition |
| title_full_unstemmed | Thrombospondin-1 induction and VEGF reduction by proteasome inhibition |
| title_short | Thrombospondin-1 induction and VEGF reduction by proteasome inhibition |
| title_sort | thrombospondin 1 induction and vegf reduction by proteasome inhibition |
| topic | Corneal vascularization Proteasome inhibition Thrombospondin-1 VEGF |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023006047 |
| work_keys_str_mv | AT fawziabardaggorce thrombospondin1inductionandvegfreductionbyproteasomeinhibition AT carterhoffman thrombospondin1inductionandvegfreductionbyproteasomeinhibition AT imarameepe thrombospondin1inductionandvegfreductionbyproteasomeinhibition AT monicaferrini thrombospondin1inductionandvegfreductionbyproteasomeinhibition AT richardhhoft thrombospondin1inductionandvegfreductionbyproteasomeinhibition AT joanoliva thrombospondin1inductionandvegfreductionbyproteasomeinhibition AT yutakaniihara thrombospondin1inductionandvegfreductionbyproteasomeinhibition |