VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathway
Diabetic retinopathy (DR) is a common microvascular complication in patients with diabetes mellitus. DR is caused by chronic hyperglycemia and is characterized by progressive loss of vision because of damage to the retinal microvasculature. In this study, we investigated the regulatory role and cli...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PAGEPress Publications
2022-10-01
|
| Series: | European Journal of Histochemistry |
| Subjects: | |
| Online Access: | https://ejh.it/index.php/ejh/article/view/3522 |
| _version_ | 1811198237028122624 |
|---|---|
| author | Meiying Zhang Min Zhou Xia Cai Yan Zhou Xueling Jiang Yan Luo Yue Hu Rong Qiu Yanrong Wu Yuejin Zhang Yan Xiong |
| author_facet | Meiying Zhang Min Zhou Xia Cai Yan Zhou Xueling Jiang Yan Luo Yue Hu Rong Qiu Yanrong Wu Yuejin Zhang Yan Xiong |
| author_sort | Meiying Zhang |
| collection | DOAJ |
| description |
Diabetic retinopathy (DR) is a common microvascular complication in patients with diabetes mellitus. DR is caused by chronic hyperglycemia and is characterized by progressive loss of vision because of damage to the retinal microvasculature. In this study, we investigated the regulatory role and clinical significance of the vascular endothelial growth factor (VEGF)/protein kinase C (PKC)/endothelin (ET)/nuclear factor-κB (NF-κB)/intercellular adhesion molecule 1 (ICAM-1) signaling pathway in DR using a rat model. Intraperitoneal injections of the VEGF agonist, streptozotocin (STZ) were used to generate the DR model rats. DR rats treated with the VEGF inhibitor (DR+VEGF inhibitor) were used to study the specific effects of VEGF on DR pathology and the underlying mechanisms. DR and DR+VEGF agonist rats were injected with the PKCβ2 inhibitor, GF109203X to determine the therapeutic potential of blocking the VEGF/PKC/ET/NF-κB/ICAM-1 signaling pathway. The body weights and blood glucose levels of the rats in all groups were evaluated at 16 weeks. DR-related retinal histopathology was analyzed by hematoxylin and eosin staining. ELISA assay was used to estimate the PKC activity in the retinal tissues. Western blotting and RT-qPCR assays were used to analyze the expression levels of PKC-β2, VEGF, ETs, NF-κB, and ICAM-1 in the retinal tissues. Immunohistochemistry was used to analyze VEGF and ICAM-1 expression in the rat retinal tissues. Our results showed that VEGF, ICAM-1, PKCβ2, ET, and NF-κB expression levels as well as PKC activity were significantly increased in the retinal tissues of the DR and DR+VEGF agonist rat groups compared to the control and DR+VEGF inhibitor rat groups. DR and DR+VEGF agonist rats showed significantly lower body weight and significantly higher retinal histopathology scores and blood glucose levels compared to the control and DR+VEGF inhibitor group rats. However, treatment of DR and DR+VEGF agonist rats with GF109203X partially alleviated DR pathology by inhibiting the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway. In summary, our data demonstrated that inhibition of the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway significantly alleviated DR-related pathology in the rat model. Therefore, VEGF/PKC/ET/NF-κB/ICAM-1 signaling axis is a promising therapeutic target for DR.
|
| first_indexed | 2024-04-12T01:27:29Z |
| format | Article |
| id | doaj.art-93b647337fac438e9dcd45ff38254b9c |
| institution | Directory Open Access Journal |
| issn | 1121-760X 2038-8306 |
| language | English |
| last_indexed | 2024-04-12T01:27:29Z |
| publishDate | 2022-10-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | European Journal of Histochemistry |
| spelling | doaj.art-93b647337fac438e9dcd45ff38254b9c2022-12-22T03:53:34ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062022-10-0166410.4081/ejh.2022.3522VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathwayMeiying Zhang0Min Zhou1Xia Cai2Yan Zhou3Xueling Jiang4Yan Luo5Yue Hu6Rong Qiu7Yanrong Wu8Yuejin Zhang9Yan Xiong10Department of Endocrinology, the Second Affiliated Hospital of Nanchang University, JiangxiDepartment of Endocrinology, the Second Affiliated Hospital of Nanchang University, JiangxiDepartment of Endocrinology, the Second Affiliated Hospital of Nanchang University, JiangxiDepartment of Endocrinology, the Second Affiliated Hospital of Nanchang University, JiangxiDepartment of Endocrinology, the Second Affiliated Hospital of Nanchang University, JiangxiDepartment of Endocrinology, the Second Affiliated Hospital of Nanchang University, JiangxiDepartment of Endocrinology, the Second Affiliated Hospital of Nanchang University, JiangxiDepartment of Endocrinology, the Second Affiliated Hospital of Nanchang University, JiangxiDepartment of Endocrinology, the Second Affiliated Hospital of Nanchang University, JiangxiDepartment of Endocrinology, the Second Affiliated Hospital of Nanchang University, JiangxiDepartment of Endocrinology, the Second Affiliated Hospital of Nanchang University, Jiangxi Diabetic retinopathy (DR) is a common microvascular complication in patients with diabetes mellitus. DR is caused by chronic hyperglycemia and is characterized by progressive loss of vision because of damage to the retinal microvasculature. In this study, we investigated the regulatory role and clinical significance of the vascular endothelial growth factor (VEGF)/protein kinase C (PKC)/endothelin (ET)/nuclear factor-κB (NF-κB)/intercellular adhesion molecule 1 (ICAM-1) signaling pathway in DR using a rat model. Intraperitoneal injections of the VEGF agonist, streptozotocin (STZ) were used to generate the DR model rats. DR rats treated with the VEGF inhibitor (DR+VEGF inhibitor) were used to study the specific effects of VEGF on DR pathology and the underlying mechanisms. DR and DR+VEGF agonist rats were injected with the PKCβ2 inhibitor, GF109203X to determine the therapeutic potential of blocking the VEGF/PKC/ET/NF-κB/ICAM-1 signaling pathway. The body weights and blood glucose levels of the rats in all groups were evaluated at 16 weeks. DR-related retinal histopathology was analyzed by hematoxylin and eosin staining. ELISA assay was used to estimate the PKC activity in the retinal tissues. Western blotting and RT-qPCR assays were used to analyze the expression levels of PKC-β2, VEGF, ETs, NF-κB, and ICAM-1 in the retinal tissues. Immunohistochemistry was used to analyze VEGF and ICAM-1 expression in the rat retinal tissues. Our results showed that VEGF, ICAM-1, PKCβ2, ET, and NF-κB expression levels as well as PKC activity were significantly increased in the retinal tissues of the DR and DR+VEGF agonist rat groups compared to the control and DR+VEGF inhibitor rat groups. DR and DR+VEGF agonist rats showed significantly lower body weight and significantly higher retinal histopathology scores and blood glucose levels compared to the control and DR+VEGF inhibitor group rats. However, treatment of DR and DR+VEGF agonist rats with GF109203X partially alleviated DR pathology by inhibiting the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway. In summary, our data demonstrated that inhibition of the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway significantly alleviated DR-related pathology in the rat model. Therefore, VEGF/PKC/ET/NF-κB/ICAM-1 signaling axis is a promising therapeutic target for DR. https://ejh.it/index.php/ejh/article/view/3522diabetic retinopathyVEGFICAM-1PKC/ET/NF-κBstreptozocin |
| spellingShingle | Meiying Zhang Min Zhou Xia Cai Yan Zhou Xueling Jiang Yan Luo Yue Hu Rong Qiu Yanrong Wu Yuejin Zhang Yan Xiong VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathway European Journal of Histochemistry diabetic retinopathy VEGF ICAM-1 PKC/ET/NF-κB streptozocin |
| title | VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathway |
| title_full | VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathway |
| title_fullStr | VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathway |
| title_full_unstemmed | VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathway |
| title_short | VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathway |
| title_sort | vegf promotes diabetic retinopathy by upregulating the pkc et nf κb icam 1 signaling pathway |
| topic | diabetic retinopathy VEGF ICAM-1 PKC/ET/NF-κB streptozocin |
| url | https://ejh.it/index.php/ejh/article/view/3522 |
| work_keys_str_mv | AT meiyingzhang vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway AT minzhou vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway AT xiacai vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway AT yanzhou vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway AT xuelingjiang vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway AT yanluo vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway AT yuehu vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway AT rongqiu vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway AT yanrongwu vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway AT yuejinzhang vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway AT yanxiong vegfpromotesdiabeticretinopathybyupregulatingthepkcetnfkbicam1signalingpathway |