Interaction of TPPP3 with VDAC1 Promotes Endothelial Injury through Activation of Reactive Oxygen Species
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
Authors: Liu, Naijia; Li, Yintao; Nan, Wu; Zhou, Wenbai; Huang, Jinya; Li, Rumei; Zhou, Linuo; Hu, Renming
Abstract
Endothelial injury plays a critical role in the pathogenesis of cardiovascular disorders and metabolic-associated vascular complications which are the leading cause of death worldwide. However, the mechanism underlying endothelial dysfunction is not completely understood. The study is aimed at investigating the role of tubulin polymerization-promoting protein family member 3 (TPPP3) in palmitic acid- (PA-) induced endothelial injury. The effect of TPPP3 on human umbilical vein endothelial cells (HUVECs) was determined by evaluating apoptosis, tube formation, and reactive oxygen species (ROS) production. TPPP3 silencing inhibited PA overload-induced apoptosis and production of ROS, along with the alteration of apoptosis-related key proteins such as BCL-2 and Bax. Mechanically, voltage-dependent anion channel 1 (VDAC1) was identified as a novel functional binding partner of TPPP3, and TPPP3 promoted VDAC1 protein stability and its activity. Further studies indicated that TPPP3 could promote apoptosis, ROS production, tube formation, and proapoptotic protein expression and reduce antiapoptotic protein expression through increasing VDAC1 expression under mildly elevated levels of PA. Collectively, these results demonstrated that TPPP3 could promote PA-induced oxidative damage in HUVECs via a VDAC1-dependent pathway, suggesting that TPPP3 might be considered as a potential therapeutic target in vascular disease.
Control the fate of human umbilical cord mesenchymal stem cells with dual-enzymatically cross-linked gelatin hydrogels for potential applications in nerve regeneration
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
Authors: Li, Jinrui; Gao, Feng; Ma, Shanshan; Zhang, Yanting; Zhang, Junni; Guan, Fangxia; Yao, Minghao
Abstract
Stem-cell-based therapy is a promising strategy to treat challenging neurological diseases, while its application is hindered primarily by the low viability and uncontrolled differentiation of stem cell. Hydrogel can be properly engineered to share similar characteristics with the target tissue, thus promoting cell viability and directing cell differentiation. In this study, we proposed a new dual-enzymatically cross-linked and injectable gelatin hydrogel for regulating survival, proliferation, and differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) in a three-dimensional matrix. This injectable gelatin hydrogel was formed by oxidative coupling of gelatin-hydroxyphenyl acid conjugates catalyzed by hydrogen horseradish peroxidase (HRP) and choline oxidase (ChOx). Modulus and H(2)O(2)release can be well controlled by ChOx activity. Results from calcein-AM/PI staining and Ki67 immunofluorescence tests demonstrated that the survival and proliferation behavior of hUC-MSCs were highly enhanced in HRP(1U)ChOx(0.25U)hydrogel with lower modulus and less H(2)O(2)release compared with other groups. Attractively, the expression of neuron-specific markers beta-III tubulin, neurofilament light chain (NFL), and synapsin-1 was significantly increased in HRP(1U)ChOx(0.25U)hydrogel as well. Additionally,in vitrohemolysis test andin vivoHE staining data highlighted the good biocompatibility. Undoubtedly, this injectable gelatin hydrogel's ability to control hUC-MSCs' fate holds enormous potentials in nervous disorders' therapy and nerve regeneration.