机构:[a]Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215006, China[b]Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Suzhou, 215123, China[c]Suzhou Yongding Hospital, Suzhou, 215200, China
Olfactory ensheathing cells (OECs) are ideal candidates for cell-based therapies aimed at repairing spinal cord injury (SCI). Accurate targeting of OECs to the lesion site is critical to reconstructing the impaired nervous system. However, the key factors guiding the homing of transplanted OECs to the damaged area after SCI are still unclear. Here, we demonstrate that lysophosphatidic acid (LPA) can significantly facilitate the homing of OECs after SCI in rats. First, we found that OECs exhibited a robust chemotaxis response to LPA in vitro, with LPAR1 being predominant receptor expressed on OECs. We further found that D-catenin signaling plays an important role in LPA-induced OEC migration. Moreover, silencing LPAR1 not only abolished the migration of OECs but also prevented ERK1/2 phosphorylation and P-catenin activation, suggesting that LPAR1 ligation serves to activate the ERK1/2 and beta-catenin pathways in LPA-induced OEC chemotactic migration. Finally, cell transplantation experiments confirmed that endogenous LPA, which was observed to be produced at the lesion site after SCI in rat, is a key chemokine that facilitates OEC migration to the injury center. Collectively, our data provide a further description of the homing effects of LPA and a mechanism by which transplanted OECs migrate to the injured area after SCI in rats.
基金:
National Natural Science Foundation of China [81271723, 51763001, 51403142, 31371407]; Preponderant Clinic Discipline Group Project Funding of the Second Affiliated Hospital of Soochow University [XKQ2015010]; Priority Academic Program Development of Jiangsu Higher Education Institutions
第一作者机构:[a]Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215006, China
共同第一作者:
通讯作者:
通讯机构:[a]Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215006, China[b]Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Suzhou, 215123, China
推荐引用方式(GB/T 7714):
Wentao Zhong,Kaipeng Bian,Ya'nan Hu,et al.Lysophosphatidic acid guides the homing of transplanted olfactory ensheathing cells to the lesion site after spinal cord injury in rats[J].EXPERIMENTAL CELL RESEARCH.2019,379(1):65-72.doi:10.1016/j.yexcr.2019.03.023.
APA:
Wentao Zhong,Kaipeng Bian,Ya'nan Hu,Zhongqing Ji,Xiaojing Xu...&Yixin Shen.(2019).Lysophosphatidic acid guides the homing of transplanted olfactory ensheathing cells to the lesion site after spinal cord injury in rats.EXPERIMENTAL CELL RESEARCH,379,(1)
MLA:
Wentao Zhong,et al."Lysophosphatidic acid guides the homing of transplanted olfactory ensheathing cells to the lesion site after spinal cord injury in rats".EXPERIMENTAL CELL RESEARCH 379..1(2019):65-72