Tissue stiffness, shear stress, and interstitial pressure make up major factors of liver mechanical microenvironment, which play the key regulatory role to control cell behaviors in the liver and progress of liver dis...Tissue stiffness, shear stress, and interstitial pressure make up major factors of liver mechanical microenvironment, which play the key regulatory role to control cell behaviors in the liver and progress of liver diseases. In this review, we focus on the characteristics of liver mechanical microenvironments and summarize cellular responses to mechanobiological changes during liver pathogenesis, especially in hepatic fibrosis and cirrhosis. A better understanding of the indispensable contributions of mechanical cues to liver homeostasis and pathogenesis is significant to identify new therapeutic targets for liver diseases such as hepatic fibrosis or cirrhosis.展开更多
Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)- mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neova...Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)- mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.展开更多
基金the Beijing Natural Science Foundation (Grant 7162210)National Key R&D Program of China (Grant 2016YFC1000810).
文摘Tissue stiffness, shear stress, and interstitial pressure make up major factors of liver mechanical microenvironment, which play the key regulatory role to control cell behaviors in the liver and progress of liver diseases. In this review, we focus on the characteristics of liver mechanical microenvironments and summarize cellular responses to mechanobiological changes during liver pathogenesis, especially in hepatic fibrosis and cirrhosis. A better understanding of the indispensable contributions of mechanical cues to liver homeostasis and pathogenesis is significant to identify new therapeutic targets for liver diseases such as hepatic fibrosis or cirrhosis.
基金the National Natural Science Foundation of China(Nos.81891002,81971178,32200806)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16040701)+2 种基金the Youth Innovation Promotion Association CAS(No.2021319)the Natural Science Foundation of Jiangsu Province(No.BK20210127)the High-level Innovation and Entrepreneurship Talent Introduction Plan of Jiangsu Province.We acknowledge the CapitalBio Technology Inc.(Beijing,China)for RNA sequencing and proteomic sequencing.Schematic in Fig.2A and 6C were created with BioRender.com and were granted publication permission.We acknowledge a kind gift of PEGDA from Prof.Y.Du(Tsinghua University,Beijing,China)and help from PhD candiate WJ.Li in his lab on schematic preparation.
文摘Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)- mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.
