1. Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. 2. Department of Ophthalmology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, China. 3. Department of Ophthalmology, People's Hospital of Yangzhong City, Yangzhong 212200, China. 4. Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. # Xinjing Wu and Bing Qin contributed equally to this work.
✉ Corresponding authors: Qinghuai Liu, Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. liuqhedu.cn. Zizhong Hu, Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. huzizhongedu.cn. Songtao Yuan, Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. yuansongtaosina.com.More
Citation:
Wu X, Qin B, Cheng R, Zhou R, Wang X, Zhang Z, Mao X, Xie Z, Chen M, Jiang L, Xie P, Ji J, Zhang W, Yuan S, Hu Z, Liu Q. Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy. Int J Biol Sci 2024; 20(3):897-915. doi:10.7150/ijbs.85735. https://www.ijbs.com/v20p0897.htm
Ocular angiogenic diseases, such as proliferative diabetic retinopathy (PDR), are often characterized by pathological new vessels and fibrosis formation. Anti-vascular endothelial growth factor (VEGF) therapy, despite of its efficiency to inhibit new vessels, has limitations, including drug resistance and retinal fibrosis. Here, we identified that Gremlin1, a novel angiogenesis and fibrosis inducer, was secreted from Müller glial cells, and its expression increased in the vitreous fluid from patients with PDR. Mechanistically, Gremlin1 triggered angiogenesis by promoting endothelial-mesenchymal transition via the EGFR/RhoA/ROCK pathway. In addition, Gremlin1 activated microglia to present profibrotic and fibrogenic properties. Further, anti-Gremlin1 antibody inhibited ocular angiogenesis and microglia fibrosis in mouse models. Collectively, Gremlin1 could be a potential therapeutic target in the treatment of ocular angiogenic diseases.
Wu, X., Qin, B., Cheng, R., Zhou, R., Wang, X., Zhang, Z., Mao, X., Xie, Z., Chen, M., Jiang, L., Xie, P., Ji, J., Zhang, W., Yuan, S., Hu, Z., Liu, Q. (2024). Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy. International Journal of Biological Sciences, 20(3), 897-915. https://doi.org/10.7150/ijbs.85735.
ACS
Wu, X.; Qin, B.; Cheng, R.; Zhou, R.; Wang, X.; Zhang, Z.; Mao, X.; Xie, Z.; Chen, M.; Jiang, L.; Xie, P.; Ji, J.; Zhang, W.; Yuan, S.; Hu, Z.; Liu, Q. Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy. Int. J. Biol. Sci. 2024, 20 (3), 897-915. DOI: 10.7150/ijbs.85735.
NLM
Wu X, Qin B, Cheng R, Zhou R, Wang X, Zhang Z, Mao X, Xie Z, Chen M, Jiang L, Xie P, Ji J, Zhang W, Yuan S, Hu Z, Liu Q. Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy. Int J Biol Sci 2024; 20(3):897-915. doi:10.7150/ijbs.85735. https://www.ijbs.com/v20p0897.htm
CSE
Wu X, Qin B, Cheng R, Zhou R, Wang X, Zhang Z, Mao X, Xie Z, Chen M, Jiang L, Xie P, Ji J, Zhang W, Yuan S, Hu Z, Liu Q. 2024. Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy. Int J Biol Sci. 20(3):897-915.
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