Journal of Cellular Physiology最新文献

RHOA, RHOB, and RHOC comprise a subfamily of RHO GTPase proteins famed for controlling cytoskeletal dynamics. RHO proteins operate downstream of multiple signals emerging from the microenvironment, leading to diverse cell responses, such as proliferation, adhesion, and migration. Therefore, RHO signaling has been centrally placed in the regulation of blood cells. Despite their high homology, unique roles of RHOA, RHOB, and RHOC have been described in hematopoietic cells. In this article, we overview the contribution of RHO proteins in the development and function of each blood cell lineage. Additionally, we highlight the aberrations of the RHO signaling pathways found in hematological malignancies, providing clues for the identification of new therapeutic targets.

Fibrosis, an aberrant reparative response to tissue injury, involves a disruption in the equilibrium between the synthesis and degradation of the extracellular matrix, leading to its excessive accumulation within normal tissues, and culminating in organ dysfunction. Manifesting in the terminal stages of nearly all chronic ailments, fibrosis carries a high mortality rate and poses a significant threat to human health. Heme oxygenase-1 (HO-1) emerges as an endogenous protective agent, mitigating tissue damage through its antioxidant, anti-inflammatory, and antiapoptotic properties. Numerous studies have corroborated HO-1's potential as a therapeutic target in anti-fibrosis treatment. This review delves into the structural and functional attributes, and the upstream and downstream pathways of HO-1. Additionally, the regulatory networks and mechanisms of HO-1 in cells associated with fibrosis are elucidated. The role of HO-1 in various fibrosis-related diseases is also explored. Collectively, this comprehensive information serves as a foundation for future research and augments the viability of HO-1 as a therapeutic target for fibrosis.

Lithospermic acid (LA) is a water-soluble phenolic acid compound extracted and separated from the dried root and the rhizome of Salviamiltiorrhiza Bge (Labiatae), possessing multiple biological activities. Firstly, in terms of pharmacological activities, LA has been proven to possess anti-inflammatory, antioxidant, autophagy activation, and antiapoptotic properties. Secondly, the pharmacokinetic characteristics of LA show rapid and extensive distribution in various tissues after intravenous administration, followed by rapid elimination and excretion. Additionally, potential therapeutic effects of LA have been found in various diseases such as thrombosis, Parkinson's disease, hepatitis B, diabetes, and psoriasis, among others. Particularly, LA has shown promising prospects in the treatment of clinical heart diseases and has been included in new drug formulations for the treatment of chronic angina, demonstrating superior efficacy compared to current cardiovascular drugs. In conclusion, this review comprehensively introduces the pharmacological mechanisms, pharmacokinetics, and protective effects in diseases of LA. These information can lay a theoretical foundation for the future development and new clinical applications of LA.

Diabetes (DM) patients have an increased risk (~50%) for sudden cardiac death (SCD), mostly as a result of ventricular arrhythmias. The molecular mechanisms involved remain partially defined. The potent proinflammatory lipid mediator leukotriene (LT) B4, is pathologically elevated in DM compared to nondiabetic patients, resulting in increased LTB4 accumulation in heart, leading to an increased risk for life-threatening proarrhythmic signatures. We used electrophysiology, immunofluorescence, and confocal microscopy approaches to evaluate LTB4 cellular effects in guinea pig heart and ventricular myocytes. We have observed that LTB4 is increased in multiple mouse models (C57BL/6 J/Lep^ob/ob and PANIC-ATTAC) of DM, promotes profound cellular arrhythmogenesis (spontaneous beats and early after depolarizations, EADs), and severely depresses the rapidly activating delayed rectifier K current (hERG1/I_Kr) density in HEK293 cells and guinea pig ventricular myocytes. We have further found that guinea pigs challenged with LTB4 displayed a significantly prolonged QT interval, and that this can be prevented with LTB4R inhibition, suggesting that preventing such LTB4R effects may be therapeutically beneficial in DM. Our data suggests that a further elucidation of LTB4 vulnerable substrates, and how this leads to ventricular arrhythmias, is likely to lead to continued improvements in management options, and the development of new therapies for prevention of SCD in DM patients.

This article corrects the following:

RA promotes proliferation of primordial germ cell-like cells differentiated from porcine skin-derived stem cells.

Hong-Chen Yan, Lin Li, Jing-Cai Liu, Yu-Feng Wang, Xue-Lian Liu, Wei Ge, Paul W. Dyce, Lan Li, Xiao-Feng Sun, Wei Shen, Shun-Feng Cheng

Volume 234, Issue 10, Journal of Cellular Physiology

https://doi.org/10.1002/jcp.28454

First published online: 11 March 2019

Volume/Issue/Pages: Journal of Cellular Physiology; 2019; 234: 18214-18229.

Correction text:

The authors recently found an error in Figure 8a in the original article, wherein an incorrect fluorescence image of Vasa staining was used. This error occurred accidentally during the selection of the representative images. The alteration does not affect the results or conclusions of Figure 8. The authors regret their error and apologize for any inconvenience to readers arising from the error.

The corrected figure is displayed below.

Legumain is a cysteine protease broadly associated with inflammation. It has been reported to cleave and activate protease-activated receptor 2 to provoke pain associated with oral cancer. Outside of gastric and colon cancer, little has been reported on the roles of legumain within the gastrointestinal tract. Using a legumain-selective activity-based probe, LE28, we report that legumain is activated within colonocytes and macrophages of the murine colon, and that it is upregulated in models of acute experimental colitis. We demonstrated that loss of legumain activity in colonocytes, either through pharmacological inhibition or gene deletion, had no impact on epithelial permeability in vitro. Moreover, legumain inhibition or deletion had no obvious impacts on symptoms or histological features associated with dextran sulfate sodium-induced colitis, suggesting its proteolytic activity is dispensable for colitis initiation. To gain insight into potential functions of legumain within the colon, we performed field asymmetric waveform ion mobility spectrometry-facilitated quantitative proteomics and N-terminomics analyses on naïve and inflamed colon tissue from wild-type and legumain-deficient mice. We identified 16 altered cleavage sites with an asparaginyl endopeptidase signature that may be direct substrates of legumain and a further 16 cleavage sites that may be indirectly mediated by legumain. We also analyzed changes in protein abundance and proteolytic events broadly associated with colitis in the gut, which permitted comparison to recent analyses on mucosal biopsies from patients with inflammatory bowel disease. Collectively, these results shed light on potential functions of legumain and highlight its potential roles in the transition from inflammation to colorectal cancer.

Vascular calcification (VC) is common in patients with advanced chronic kidney disease (CKD).A series of factors, such as calcium and phosphorus metabolism disorders, uremic toxin accumulation, inflammation and oxidative stress and cellular senescence, cause osteoblast-like differentiation of vascular smooth muscle cells, secretion of extracellular vesicles, and imbalance of calcium regulatory factors, which together promote the development of VC in CKD. Recent advances in epigenetics have provided better tools for the investigation of VC etiology and new approaches for finding more accurate biomarkers. These advances have not only deepened our understanding of the pathophysiological mechanisms of VC in CKD, but also provided valuable clues for the optimization of clinical predictors and the exploration of potential therapeutic targets. The aim of this article is to provide a comprehensive overview of the pathogenesis of CKD VC, especially the new advances made in recent years, including the various key factors mentioned above. Through the comprehensive analysis, we expect to provide a solid theoretical foundation and research direction for future studies targeting the specific mechanisms of CKD VC, the establishment of clinical predictive indicators and the development of potential therapeutic strategies.

The overexpression of major histocompatibility complex (MHC) I on the surface of muscle fibers is a characteristic hallmark of the idiopathic inflammatory myopathies (IIMs), collectively termed myositis. Alongside MHC-I overexpression, subtypes of myositis, display a distinct type I interferon (IFN) signature. This study examined the combinational effects of elevated MHC-I and type I IFNs (IFNα/β) on mitochondrial function, as mitochondrial dysfunction is often seen in IIMs. Human skeletal muscle myoblasts were transfected with an MHC-I isoform using the mammalian HLA-A2/K^b vector. Mitochondrial respiration, mitochondrial membrane potential, and reactive oxygen/nitrogen species generation were assessed with or without IFNα and IFNβ. We show that MHC-I overexpression in human skeletal muscle myoblasts led to decreased basal glycolysis and mitochondrial respiration, cellular spare respiratory capacity, adenosine triphosphate-linked respiration, and an increased proton leak, which were all exaggerated by type I IFNs. Mitochondrial membrane depolarization was induced by MHC-I overexpression both in absence and presence of type I IFNs. Human myoblasts overexpressing MHC-I showed elevated nitric oxide generation that was abolished when combined with IFN. MHC-I on its own did not result in an increased reactive oxygen species (ROS) production, but IFN on their own, or combined with MHC-I overexpression did induce elevated ROS generation. Surprisingly, we observed no gross changes in mitochondrial reticular structure or markers of mitochondrial dynamics. We present new evidence that MHC-I overexpression and type I IFNs aggravate the effects each has on mitochondrial function in human skeletal muscle cells, providing novel insights into their mechanisms of action and suggesting important implications in the further study of myositis pathogenesis.

Increased prevalence of skin ageing is a growing concern due to an ageing global population and has both sociological and psychological implications. The use of more clinically predictive in vitro methods for dermatological research is becoming commonplace due to initiatives and the cost of clinical testing. In this study, we utilise a well-defined and characterised bioengineered skin construct as a tool to investigate the cellular and molecular dynamics involved in skin ageing from a dermal perspective. Through incorporation of ageing fibroblasts into the dermal compartment we demonstrate the significant impact of dermal-epidermal crosstalk on the overlying epidermal epithelium. We characterise the paracrine nature of dermal-epidermal communication and the impact this has during skin ageing. Soluble factors, such as inflammatory cytokines released as a consequence of senescence associated secretory phenotype (SASP) from ageing fibroblasts, are known to play a pivotal role in skin ageing. Here, we demonstrate their effect on epidermal morphology and thickness, but not keratinocyte differentiation or tissue structure. Through a novel in vitro strategy utilising bioengineered tissue constructs, this study offers a unique reductionist approach to study epidermal and dermal compartments in isolation and tandem.