Int J Biol Sci 2018; 14(2):178-188. doi:10.7150/ijbs.24074
MicroRNA-21-5p mediates TGF-β-regulated fibrogenic activation of spinal fibroblasts and the formation of fibrotic scars after spinal cord injury
1. Jinan Central Hospital Affiliated to Shandong University, No. 105, Jiefang Road, Jinan, Shandong, 250013, China;
2. Affiliated Hospital of Taishan Medical University, No. 706, Taishan Street, Taian, Shandong, 271000, China.
Little regeneration of transected axons occurs after the damage caused by traumatic spinal cord injury (SCI), and unidirectional and irreversible fibrotic scars are thought to be the main chemical and physical obstacle for axonal regrowth in SCI pathology. We previously demonstrated that microRNA (miR)-21-5p and transforming growth factor (TGF)-β1, a central pathological mediator of fibrotic diseases, were significantly up-regulated in the lesion epicenter after SCI. Here, we found that TGF-β1 enhanced miR-21-5p expression in primary spinal fibroblasts, and regulated the expression of fibrosis-related genes. The overexpression of miR-21-5p promoted the pro-fibrogenic activity of TGF-β1 in spinal fibroblasts, while miR-21-5p knockdown attenuated this activity. We identified Smad7 as a target gene of miR-21-5p, suggesting a potential mechanism for the role of miR-21-5p in spinal fibrosis through regulating Smad7 expression. Furthermore, miR-21-5p knockdown in a mouse model significantly improved motor functional recovery after spinal cord injury. These data demonstrate that miR-21-5p functions in an amplifying circuit to enhance TGF-β signaling events in the activation of spinal fibroblasts and suggest that miR-21-5p is a potential therapeutic target in the treatment of fibrotic scar formation after SCI.
Keywords: spinal cord injury, microRNA-21, signaling pathway, fibrotic scar
Wang W, Liu R, Su Y, Li H, Xie W, Ning B. MicroRNA-21-5p mediates TGF-β-regulated fibrogenic activation of spinal fibroblasts and the formation of fibrotic scars after spinal cord injury. Int J Biol Sci 2018; 14(2):178-188. doi:10.7150/ijbs.24074. Available from http://www.ijbs.com/v14p0178.htm