Project description:Asthma is a chronic inflammatory airway disease characterized by airway inflammation and remodeling. The role of 15-oxo-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-oxoETE), a 15-HETE metabolite catalyzed by 15-prostaglandin dehydrogenase (15-PGDH), has been relatively unexplored in asthma. In this study, we used RNA-seq to explore the effect of 15-KETE on the transcriptome of airway epithelial cells, aiming to identify its potential downstream targets and mechanisms of action.
Project description:Aging impacts on the plasticity and biochemistry of skeletal muscle. For a deeper understanding of skeletal muscle function in aging and sarcopenia, defined as age related muscle decline, the identification of molecular signatures regulating muscle function under physiological conditions is important. While molecular studies of healthy skeletal muscle in humans were performed in adults and older subjects, skeletal muscle from infants are poorly investigated in terms of combined morphological, transcriptomic and proteomic profiles.
Project description:Aging impairs skeletal muscle insulin sensitivity, yet the underlying molecular mechanisms remain incompletely understood. Here, we examined how short-term caloric restriction (CR) alters muscle insulin action and signaling in aged rats (22 months old) of both sexes. After 8 weeks of CR or ad libitum feeding, we assessed insulin-stimulated glucose uptake (ISGU) ex vivo and performed deep phosphoproteomic profiling. CR enhanced ISGU in both sexes, with a more pronounced effect in females. Insulin-regulated phosphoproteomic responses were concordant between males and females, yet females exhibited more robust and widespread phosphorylation changes, potentially explaining their greater ISGU. CR induced extensive remodeling of basal muscle phosphorylation, particularly within structural and contractile pathways. Personalized phosphoproteomic analysis identified insulin-responsive sites on Leiomodin-1 (Lmod1) and EH domain-binding protein 1-like protein 1 (Ehbp1l1) that correlated with ISGU across individuals. Notably, Lmod1demonstrated strong genetic association with glycemic traits in humans, and several regulated sites overlapped with phosphosites observed in human clamp studies, reinforcing their translational relevance. Collectively, these findings reveal sex-dependent and diet-sensitive phosphosignaling mechanisms that modulate muscle insulin responsiveness during aging and nominate candidate regulatory nodes for future study.
Project description:Women’s aging is characterized by menopausal loss of ovarian function, which has been suggested as a contributing factor to aging-related muscle deterioration and predisposes to the metabolic dysfunctions. However, the underlying molecular mechanisms have remained unknown. To identify mechanisms, we utilized muscle samples from 24 pre- and postmenopausal women, established proteome-wide profiles and identified upstream regulators and downstream cellular pathways associated with the differences in age, menopausal status and use of hormone replacement therapy (HRT). None of the premenopausal women used hormonal medication while the postmenopausal women were monozygotic twin-sister pairs who were either current HRT users or had never used HRT. The proteomic analyses resulted in the quantification of 762 muscle proteins of which 158 were for the first time associated with female muscle aging. The Ingenuity Pathway Analysis pinpointed 17β-estradiol as a potential upstream regulator of the observed differences in the major downstream pathways including dysregulated cell death and glycolysis pathways. The results increase knowledge on the factors related to skeletal muscle signaling and aging. This is of importance, since the role of female sex hormones in the regulation of muscle cell signaling has been under appreciated and scarcely studied as compared to vast amount of data on male sex hormones and skeletal muscle. Our results clearly demonstrate the also female sex hormones and HRT should be considered as potential active players and an intervention targets to promote women’s muscular health.