MicroRNA-21-5p mediates TGF-β-regulated fibrogenic activation of spinal fibroblasts and the formation of fibrotic scars after spinal cord injury

International Journal of Biological Sciences
Wenzhao WangBin Ning

Abstract

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 potenti...Continue Reading

Citations

Apr 2, 2020·World Journal of Gastroenterology : WJG·Diana Gabriela IacobSimona Maria Ruta
Feb 23, 2019·Acta neurologica Belgica·Fang Li, Mou-Wang Zhou
Oct 23, 2019·Advances in Wound Care·Pinghui ZhouWenguo Cui
Feb 26, 2020·Molecular Biology Reports·Liang ZhangTianyi Wang
Jun 26, 2020·Scientific Reports·Mariam Y El-HattabEdward A Sander
Mar 2, 2021·Neural Regeneration Research·Wen-Zhao WangXiao-Ling Hou
Feb 19, 2021·Frontiers in Neuroscience·Pei LiJingjing Jiang
Apr 4, 2021·International Journal of Molecular Sciences·Carolina Kymie Vasques NonakaMilena Botelho Pereira Soares
May 5, 2021·Stroke; a Journal of Cerebral Circulation·Lingling Xu, Yao Yao
May 7, 2021·Regenerative Medicine·Xu-Dong GuoXue-Wen Kang
May 16, 2021·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Wenzhao WangWei Xie
Aug 8, 2021·International Journal of Molecular Sciences·Tomoko TadokoroTsutomu Masaki

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Methods Mentioned

BETA
transfection
PCR
electrophoresis

Software Mentioned

GraphPad Prism
PicTar
miRanda
SPSS
KEGG Pathway
TargetScan

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