Browsing by Author "Wang, Chaojian"

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    Desmin interacts with STIM1 and coordinates Ca2+ signaling in skeletal muscle.
    (JCI insight, 2021-09) Zhang, Hengtao; Bryson, Victoria Graham; Wang, Chaojian; Li, TianYu; Kerr, Jaclyn P; Wilson, Rebecca; Muoio, Deborah M; Bloch, Robert J; Ward, Christopher; Rosenberg, Paul B
    Stromal interaction molecule 1 (STIM1), the sarcoplasmic reticulum (SR) transmembrane protein, activates store-operated Ca2+ entry (SOCE) in skeletal muscle and, thereby, coordinates Ca2+ homeostasis, Ca2+-dependent gene expression, and contractility. STIM1 occupies space in the junctional SR membrane of the triads and the longitudinal SR at the Z-line. How STIM1 is organized and is retained in these specific subdomains of the SR is unclear. Here, we identified desmin, the major type III intermediate filament protein in muscle, as a binding partner for STIM1 based on a yeast 2-hybrid screen. Validation of the desmin-STIM1 interaction by immunoprecipitation and immunolocalization confirmed that the CC1-SOAR domains of STIM1 interact with desmin to enhance STIM1 oligomerization yet limit SOCE. Based on our studies of desmin-KO mice, we developed a model wherein desmin connected STIM1 at the Z-line in order to regulate the efficiency of Ca2+ refilling of the SR. Taken together, these studies showed that desmin-STIM1 assembles a cytoskeletal-SR connection that is important for Ca2+ signaling in skeletal muscle.
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    Inhalation of an RNA aptamer that selectively binds extracellular histones protects from acute lung injury.
    (Molecular therapy. Nucleic acids, 2023-03) Lei, Beilei; Wang, Chaojian; Snow, Kamie; Graton, Murilo E; Tighe, Robert M; Fager, Ammon M; Hoffman, Maureane R; Giangrande, Paloma H; Miller, Francis J
    Acute lung injury (ALI) is a syndrome of acute inflammation, barrier disruption, and hypoxemic respiratory failure associated with high morbidity and mortality. Diverse conditions lead to ALI, including inhalation of toxic substances, aspiration of gastric contents, infection, and trauma. A shared mechanism of acute lung injury is cellular toxicity from damage-associated molecular patterns (DAMPs), including extracellular histones. We recently described the selection and efficacy of a histone-binding RNA aptamer (HBA7). The current study aimed to identify the effects of extracellular histones in the lung and determine if HBA7 protected mice from ALI. Histone proteins decreased metabolic activity, induced apoptosis, promoted proinflammatory cytokine production, and caused endothelial dysfunction and platelet activation in vitro. HBA7 prevented these effects. The oropharyngeal aspiration of histone proteins increased neutrophil and albumin levels in bronchoalveolar lavage fluid (BALF) and precipitated neutrophil infiltration, interstitial edema, and barrier disruption in alveoli in mice. Similarly, inhaling wood smoke particulate matter, as a clinically relevant model, increased lung inflammation and alveolar permeability. Treatment by HBA7 alleviated lung injury in both models of ALI. These findings demonstrate the pulmonary delivery of HBA7 as a nucleic acid-based therapeutic for ALI.
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    SOCE in the cardiomyocyte: the secret is in the chambers.
    (Pflugers Archiv : European journal of physiology, 2021-03) Rosenberg, Paul; Zhang, Hengtao; Bryson, Victoria Graham; Wang, Chaojian
    Store-operated Ca2+ entry (SOCE) is an ancient and ubiquitous Ca2+ signaling pathway that is present in virtually every cell type. Over the last two decades, many studies have implicated this non-voltage dependent Ca2+ entry pathway in cardiac physiology. The relevance of the SOCE pathway in cardiomyocytes is often questioned given the well-established role for excitation contraction coupling. In this review, we consider the evidence that STIM1 and SOCE contribute to Ca2+ dynamics in cardiomyocytes. We discuss the relevance of this pathway to cardiac growth in response to developmental and pathologic cues. We also address whether STIM1 contributes to Ca2+ store refilling that likely impacts cardiac pacemaking and arrhythmogenesis in cardiomyocytes.