Select Septate Junction Proteins Direct ROS-Mediated Paracrine Regulation of Drosophila Cardiac Function

Lim, Hui‐Ying; Bao, Hong; Liu, Ying; Wang, Weidong

doi:10.1016/j.celrep.2019.07.004

Cited by 7 publications

(7 citation statements)

References 64 publications

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“…Our study unravels the mechanistic basis of a metabolic role of the PCs, quite distinct from their normal nephrocytic function, in regulating cardiac activity in Drosophila . Studies in the recent past identified that elevated levels of pericardial ROS, in a p38-dependent manner, regulates the function of the neighboring cardiomyocytes involving two septate junction proteins, Cora and Kune ( 46 ). However, the underlying mechanism remains elusive.…”

Section: Discussionmentioning

confidence: 99%

Physiological ROS controls Upd3-dependent modeling of ECM to support cardiac function in Drosophila

et al. 2022

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Despite their highly reactive nature, reactive oxygen species (ROS) at the physiological level serve as signaling molecules regulating diverse biological processes. While ROS usually act autonomously, they also function as local paracrine signals by diffusing out of the cells producing them. Using in vivo molecular genetic analyses in Drosophila , we provide evidence for ROS-dependent paracrine signaling that does not entail ROS release. We show that elevated levels of physiological ROS within the pericardial cells activate a signaling cascade transduced by Ask1, c-Jun N-terminal kinase, and p38 to regulate the expression of the cytokine Unpaired 3 (Upd3). Upd3 released by the pericardial cells controls fat body–specific expression of the extracellular matrix (ECM) protein Pericardin, essential for cardiac function and healthy life span. Therefore, our work reveals an unexpected inter-organ communication circuitry wherein high physiological levels of ROS regulate cytokine-dependent modulation of cardiac ECM with implications in normal and pathophysiological conditions.

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Section: Discussionmentioning

confidence: 99%

Physiological ROS controls Upd3-dependent modeling of ECM to support cardiac function in Drosophila

et al. 2022

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“…Somewhat surprisingly, many SJ proteins are also required for the development of the dorsal vessel (heart), even though there is no SJ formed in this tissue [ 74 ]. The Drosophila embryonic heart is a linear organ composed of two rows of cardiomyocytes, the cells which contract to pump hemolymph through the organism, surrounded by two layers of pericardial cells, which have secretory, regulatory, and filtration roles [ 75 , 76 , 77 , 78 , 79 ]. Although SJs are not found in the dorsal vessel, two clear roles within the dorsal vessel have emerged for SJ proteins: in cell-cell adhesion and as effectors of reactive oxygen species-mediated paracrine regulation of cardiac function [ 77 , 80 ].…”

Section: Developmental Functions Of Sj Genesmentioning

confidence: 99%

“…In addition to the adhesive roles played by this wide set of SJ proteins, a critical role in regulating the structure and function of the dorsal vessel has been identified for a much smaller set of SJ proteins: Cora and the claudin Kune. These proteins were identified as sensitive to levels of reactive oxygen species (ROS) in pericardial cells, a characteristic not possessed by any of the other SJ proteins tested, nor by other members of the Protein 4.1 family [ 77 ]. The ROS signaling cascade acts through proteins such as the p38a MAP kinase in the pericardial cells to regulate critical processes in the neighboring cardiomyocytes [ 82 ].…”

Section: Developmental Functions Of Sj Genesmentioning

confidence: 99%

“…The ROS signaling cascade acts through proteins such as the p38a MAP kinase in the pericardial cells to regulate critical processes in the neighboring cardiomyocytes [ 82 ]. Cora acts downstream of p38a and relies upon p38a for proper levels of protein expression [ 77 ]. In turn, Cora regulates expression of Kune, with higher levels of Cora resulting in lower levels of Kune and vice versa.…”

Section: Developmental Functions Of Sj Genesmentioning

confidence: 99%

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Expanding the Junction: New Insights into Non-Occluding Roles for Septate Junction Proteins during Development

Rice

Alhadyian

et al. 2021

JDB

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The septate junction (SJ) provides an occluding function for epithelial tissues in invertebrate organisms. This ability to seal the paracellular route between cells allows internal tissues to create unique compartments for organ function and endows the epidermis with a barrier function to restrict the passage of pathogens. Over the past twenty-five years, numerous investigators have identified more than 30 proteins that are required for the formation or maintenance of the SJs in Drosophila melanogaster, and have determined many of the steps involved in the biogenesis of the junction. Along the way, it has become clear that SJ proteins are also required for a number of developmental events that occur throughout the life of the organism. Many of these developmental events occur prior to the formation of the occluding junction, suggesting that SJ proteins possess non-occluding functions. In this review, we will describe the composition of SJs, taking note of which proteins are core components of the junction versus resident or accessory proteins, and the steps involved in the biogenesis of the junction. We will then elaborate on the functions that core SJ proteins likely play outside of their role in forming the occluding junction and describe studies that provide some cell biological perspectives that are beginning to provide mechanistic understanding of how these proteins function in developmental contexts.

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“…New lines of evidence show that ROS signaling can be transferred in a diffusion-independent fashion from donor cells to nearby cells [135]. For instance, pericardial ROS were shown to directly modulate the expression of cell adhesion and cytoskeleton molecules that facilitate interaction between the pericardial cells and cardiac myocytes [136]. In addition, extracellular vesicles such as exosomes that derived from CMs in response to H 2 O 2 were shown to exacerbate apoptosis of transplanted stem cells [137].…”

Section: New Insights Of Ros In Intercellular Communicationsmentioning

confidence: 99%

Roles of Reactive Oxygen Species in Cardiac Differentiation, Reprogramming, and Regenerative Therapies

Liang

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Reactive oxygen species (ROS) have been implicated in mechanisms of heart development and regenerative therapies such as the use of pluripotent stem cells. The roles of ROS mediating cell fate are dependent on the intensity of stimuli, cellular context, and metabolic status. ROS mainly act through several targets (such as kinases and transcription factors) and have diverse roles in different stages of cardiac differentiation, proliferation, and maturation. Therefore, further detailed investigation and characterization of redox signaling will help the understanding of the molecular mechanisms of ROS during different cellular processes and enable the design of targeted strategies to foster cardiac regeneration and functional recovery. In this review, we focus on the roles of ROS in cardiac differentiation as well as transdifferentiation (direct reprogramming). The potential mechanisms are discussed in regard to ROS generation pathways and regulation of downstream targets. Further methodological optimization is required for translational research in order to robustly enhance the generation efficiency of cardiac myocytes through metabolic modulations. Additionally, we highlight the deleterious effect of the host’s ROS on graft (donor) cells in a paracrine manner during stem cell-based implantation. This knowledge is important for the development of antioxidant strategies to enhance cell survival and engraftment of tissue engineering-based technologies. Thus, proper timing and level of ROS generation after a myocardial injury need to be tailored to ensure the maximal efficacy of regenerative therapies and avoid undesired damage.

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Select Septate Junction Proteins Direct ROS-Mediated Paracrine Regulation of Drosophila Cardiac Function

Cited by 7 publications

References 64 publications

Physiological ROS controls Upd3-dependent modeling of ECM to support cardiac function in Drosophila

Physiological ROS controls Upd3-dependent modeling of ECM to support cardiac function in Drosophila

Expanding the Junction: New Insights into Non-Occluding Roles for Septate Junction Proteins during Development

Roles of Reactive Oxygen Species in Cardiac Differentiation, Reprogramming, and Regenerative Therapies

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