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Xiaoxi Yang Chuiguo Sun Xiangyu Meng Guanghui Chen Tianqi Fan Chi Zhang Zhongqiang Chen 《Journal of cellular and molecular medicine》2022,26(14):3862
Thoracic ossification of the ligamentum flavum (TOLF) is ectopic ossification of the spinal ligaments. Histologically, the development of TOLF can be described as the process of endochondral ossification. However, the underlying aetiology has not been completely clarified. In this investigation, the gene expression profile associated with leucine‐rich repeat‐containing G‐protein‐coupled receptors (LGR) and Wnt signalling pathway in the thoracic ligamentum flavum cells (TLFCs) of different ossification stages was analysed via RNA sequencing. We further confirmed the significant differences in the related gene expression profile by Gene Ontology (GO) enrichment analysis. LGR5 was first identified in primary human TLFCs during osteogenic differentiation. To evaluate the effect of LGR5 on osteogenic differentiation, LGR5 has been knocked down and overexpressed in human TLFCs. We observed that the knockdown of LGR5 inhibited the activity of Wnt signalling and attenuated the potential osteogenic differentiation of TLFCs, while overexpression of LGR5 activated the Wnt signalling pathway and increased osteogenic differentiation. Our results provide important evidence for the potent positive mediatory effects of LGR5 on osteogenesis by enhancing the Wnt signalling pathway in TOLF. 相似文献
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LRG‐1 promotes fat graft survival through the RAB31‐mediated inhibition of hypoxia‐induced apoptosis
Chiakang Ho Danning Zheng Jiaming Sun Dongsheng Wen Shan Wu Li Yu Ya Gao Yifan Zhang Qingfeng Li 《Journal of cellular and molecular medicine》2022,26(11):3153
Autologous adipose tissue is an ideal soft tissue filling material, and its biocompatibility is better than that of artificial tissue substitutes, foreign bodies and heterogeneous materials. Although autologous fat transplantation has many advantages, the low retention rate of adipose tissue limits its clinical application. Here, we identified a secretory glycoprotein, leucine‐rich‐alpha‐2‐glycoprotein 1 (LRG‐1), that could promote fat graft survival through RAB31‐mediated inhibition of hypoxia‐induced apoptosis. We showed that LRG‐1 injection significantly increased the maintenance of fat volume and weight compared with the control. In addition, higher fat integrity, more viable adipocytes and fewer apoptotic cells were observed in the LRG‐1‐treated groups. Furthermore, we discovered that LRG‐1 could reduce the ADSC apoptosis induced by hypoxic conditions. The mechanism underlying the LRG‐1‐mediated suppression of the ADSC apoptosis induced by hypoxia was mediated by the upregulation of RAB31 expression. Using LRG‐1 for fat grafts may prove to be clinically successful for increasing the retention rate of transplanted fat. 相似文献
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Phosphorylation on tyrosine-15 of p34(Cdc2) by ErbB2 inhibits p34(Cdc2) activation and is involved in resistance to taxol-induced apoptosis 总被引:4,自引:0,他引:4
Tan M Jing T Lan KH Neal CL Li P Lee S Fang D Nagata Y Liu J Arlinghaus R Hung MC Yu D 《Molecular cell》2002,9(5):993-1004
ErbB2 overexpression confers resistance to taxol-induced apoptosis by inhibiting p34(Cdc2) activation. One mechanism is via ErbB2-mediated upregulation of p21(Cip1), which inhibits Cdc2. Here, we report that the inhibitory phosphorylation on Cdc2 tyrosine (Y)15 (Cdc2-Y15-p) is elevated in ErbB2-overexpressing breast cancer cells and primary tumors. ErbB2 binds to and colocalizes with cyclin B-Cdc2 complexes and phosphorylates Cdc2-Y15. The ErbB2 kinase domain is sufficient to directly phosphorylate Cdc2-Y15. Increased Cdc2-Y15-p in ErbB2-overexpressing cells corresponds with delayed M phase entry. Expressing a nonphosphorylatable mutant of Cdc2 renders cells more sensitive to taxol-induced apoptosis. Thus, ErbB2 membrane RTK can confer resistance to taxol-induced apoptosis by directly phosphorylating Cdc2. 相似文献