Biology subjects

Park, K.-s.

Publications and source records attributed to Park, K.-s..

2 recordsLinked to original sources

bioRxiv2026

Orai1-mediated Ca2+ Entry Regulates Lipolysis and Mitochondrial Activation in Brown Adipose Thermogenesis

Cold-induced thermogenesis in brown adipose tissue (BAT) is essential for maintaining energy homeostasis, yet the Ca2+-dependent mechanisms underlying this process remain incompletely understood. Here, we identify Orai1, a component of the store-operated Ca2+ entry pathway, as a regulator of thermogenic activation in BAT. Using a brown adipocyte-specific Orai1 knockout mouse model, we demonstrate that cold exposure is associated with Orai1-dependent Ca2+ influx through a non-canonical mechanism. Orai1 deficiency leads to impaired cAMP-PKA signaling, reduces the expression of lipolytic enzymes and thermogenic genes, and diminished mitochondrial Ca2+ uptake and uncoupling. These defects culminate in cold intolerance, lipid accumulation, and decreased energy expenditure. Mechanistically, Orai1 facilitates Ca2+-dependent activation of adenylyl cyclase 3, linking membrane Ca2+ entry to cAMP production, and promotes mitochondrial remodeling and oxidative metabolism. These findings support a key role for Orai1 in coordinating Ca2+ entry to lipolytic and mitochondrial pathways in brown adipocytes and highlight its potential therapeutic target in metabolic diseases characterized by impaired energy metabolism. HIGHLIGHTSO_LIOrai1 mediates Ca2+ influx in brown adipocytes through a non-canonical, partially STIM1-independent mechanism. C_LIO_LIOrai1-mediated Ca2+ influx promotes both cAMP-PKA-driven lipolysis and mitochondrial oxidative activation. C_LIO_LIOrai1-dependent Ca2+ entry promotes cAMP-PKA signaling and lipolytic activation I nbrown adipocytes. C_LIO_LIOrai1 coordinates mitochondrial Ca2+ uptake to support thermogenic function in brown adipocytes. C_LI

physiology↗

bioRxiv2026

Extracellular Vesicle-Enriched Secretome from Mesenchymal Stromal Cells Protects Against Chemically, Particulate-, and Ischemia-Induced Innate-Immunity Induced Inflammation

Mesenchymal stromal cells (MSCs) are multipotent cells with well-established regenerative and immunomodulatory properties, making them promising candidates for the treatment of inflammatory diseases. However, the therapeutic effects of MSCs are largely mediated by their secretome, particularly extracellular vesicles (EVs), which deliver bioactive molecules capable of modulating inflammatory responses. We generated an extracellular vesicle-enriched secretome (EVES) from MSCs under scalable, Good Manufacturing Practice (GMP)-compliant conditions and assessed its therapeutic efficacy in diverse disease models, including lung inflammation and kidney injury induced by distinct innate immune stimuli. EVES was isolated from the secretome of umbilical cord blood-derived MSCs cultured in a chemically defined medium. In vitro, EVES significantly and dose-dependently attenuated cytokine release from airway epithelial cells and macrophages stimulated with inflammatory agents such as lipopolysaccharide or reactive particles. In murine models of lung inflammation, EVES reduced neutrophil infiltration and suppressed multiple cytokines and chemokines in a dose-dependent manner. In models of kidney injury, EVES enhanced tubular epithelial cell proliferation, improved renal histology, and markedly reduced tubular necrosis following ischemia-reperfusion injury. Collectively, these findings demonstrate that MSC-derived EVES exhibits robust and broad-spectrum therapeutic activity across multiple disease contexts driven by innate immune activation, supporting its potential as a scalable, cell-free therapeutic platform.

cell biology↗