RESUMO
Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo.
Assuntos
RNA Polimerases Dirigidas por DNA , Células Endoteliais da Veia Umbilical Humana , Mitocôndrias , Humanos , Animais , Camundongos , Mitocôndrias/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , RNA Polimerases Dirigidas por DNA/genética , Retinopatia Diabética/patologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/genética , Camundongos Endogâmicos C57BL , Proliferação de Células , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Masculino , Neovascularização Fisiológica/genética , Movimento Celular , Apoptose , AngiogêneseRESUMO
The research reported in this article clarifies how employee-organization relationships (EORs) work. Specifically, the authors tested whether social exchange and job embeddedness mediate how mutual-investment (whereby employers offer high inducements to employees for their high contributions) and over-investment (high inducements without corresponding high expected contributions) EOR approaches, which are based on Tsui, Pearce, Porter, and Tripoli's (1997) framework, affect quit propensity and organizational commitment. Two studies evaluated these intervening mechanisms. Study 1 surveyed 953 Chinese managers attending part-time master of business administration (MBA) programs in China, whereas Study 2 collected cross-sectional and longitudinal data from 526 Chinese middle managers in 41 firms. Standard and multilevel causal modeling techniques affirmed that social exchange and job embeddedness translate EOR influence. A second multilevel test using lagged outcome measures further established that job embeddedness mediates long-term EOR effects over 18 months. These findings corroborate prevailing views that social exchange explains how mutual- and over-investment EORs motivate greater workforce commitment and loyalty. This study enriches EOR perspectives by identifying job embeddedness as another mediator that is more enduring than social exchange.
Assuntos
Planos para Motivação de Pessoal , Relações Interpessoais , Satisfação no Emprego , Lealdade ao Trabalho , Gestão de Recursos Humanos/métodos , Adulto , China , Estudos Transversais , Coleta de Dados , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Objetivos Organizacionais , Reorganização de Recursos HumanosRESUMO
This study examined the roles of 3 multilevel motivational predictors in protégés' personal learning in teams: an autonomy-supportive team climate, mentors' autonomy support, and protégés' autonomy orientation. The authors followed 305 protégés in 58 teams for 12 weeks and found that all 3 predictors were positively related to the protégés' personal learning in teams and that an autonomy-supportive team climate augmented the effects of mentors' autonomy support and protégés' autonomy orientation on protégés' personal learning in teams. Protégés' personal learning in teams mediated the interactive effects of an autonomy-supportive team climate with mentors' autonomy support or protégés' autonomy orientation on protégés' behavioral and attitudinal outcomes, including their organizational citizenship behaviors and job involvement. The findings of this study provide business researchers and practitioners with valuable insights into the management of autonomy.