BMB Reports最新文献

Epigenetic alterations play a crucial role in developmental processes, tissue regeneration, and cellular differentiation. Epigenetic changes are dynamically reversible. Various drugs that target DNA methyltransferases or histone deacetylases have demonstrated their ability to restore normal epigenetic patterns in a number of diseases. While the involvement of epigenetic modifications has been identified in chronic inflammatory diseases, their specific impact on skin inflammation in stromal cells remains unclear. This mini-review explores the role of stromal cells in chronic inflammatory skin diseases, focusing on epigenetic modifications of stromal cells such as fibroblasts, lymphatic, and blood vascular endothelial cells in both healthy and diseased skin. We also provide an overview of recent findings that highlight the contribution of stromal cells, including fibroblasts, to inflammatory and remodeling processes through epigenetic changes in the context of chronic inflammatory conditions. Investigating epigenetic reprogramming of stromal cells might lead to novel strategies for treating chronic inflammatory skin diseases.

Matricellular proteins are integral non-structural components of the extracellular matrix. They serve as essential modulators of immunometabolism and tissue homeostasis, playing critical roles in physiological and pathological conditions. These extracellular matrix proteins including thrombospondins, osteopontin, tenascins, the secreted protein acidic and rich in cysteine (SPARC) family, the Cyr61, CTGF, NOV (CCN) family, and fibulins have multi-faceted functions in regulating immune cell functions, metabolic pathways, and tissue homeostasis. They are involved in immune-metabolic regulation and influence processes such as insulin signaling, adipogenesis, lipid metabolism, and immune cell function, playing significant roles in metabolic disorders such as obesity and diabetes. Furthermore, their modulation of tissue homeostasis processes including cellular adhesion, differentiation, migration, repair, and regeneration is instrumental for maintaining tissue integrity and function. The importance of these proteins in maintaining physiological equilibrium is underscored by the fact that alterations in their expression or function often coincide with disease manifestation. This review contributes to our growing understanding of these proteins, their mechanisms, and their potential therapeutic applications. [BMB Reports 2024; 57(9): 400-416].

Collagen type III, a member of the fibrillar collagen group, is a major component of the extracellular matrix in various internal organs, the vascular systems, and skin. It is essential to maintain the structural integrity and functionality of these tissues, and plays a significant role in wound healing, often found alongside collagen type I. Despite being the second most abundant collagen in human tissues after type I, its biological functions on various skin properties have not been thoroughly studied. In this study, we have isolated and developed an effective recombinant protein derived from human collagen type III alpha 1 chain (hCOL3A1). Our findings demonstrate that the recombinant proteins hCOL3A1-THR-M1 and M4 stimulate cell proliferation and collagen biosynthesis in human dermal fibroblasts (HDFs), and enhance wound healing. Notably, hCOL3A1-THR- M1 (referred to as HUCOLLATIN3) specifically penetrates both the epidermal and dermal layers in a full-thickness skin model. These results collectively indicate that hCOL3A1-THR-M1 holds promise as a potential biomaterial to prevent skin aging. [BMB Reports 2024; 57(9): 424-429].

The nucleus, a highly organized and dynamic organelle, plays a crucial role in regulating cellular processes. During cell differentiation, profound changes occur in gene expression, chromatin organization, and nuclear morphology. This review explores the intricate relationship between nuclear architecture and cellular function, focusing on the roles of the nuclear lamina, nuclear pore complexes (NPCs), sub-nuclear bodies, and the nuclear scaffold. These components collectively maintain nuclear integrity, organize chromatin, and interact with key regulatory factors. The dynamic remodeling of chromatin, its interactions with nuclear structures, and epigenetic modifications work in concert to modulate gene accessibility and ensure precise spatiotemporal control of gene expression. The nuclear lamina stabilizes nuclear shape and is associated with inactive chromatin regions, while NPCs facilitate selective transport. Sub-nuclear bodies contribute to genome organization and gene regulation, often by influencing RNA processing. The nuclear scaffold provides structural support, impacting 3D genome organization, which is crucial for proper gene expression during differentiation. This review underscores the significance of nuclear architecture in regulating gene expression and guiding cell differentiation. Further investigation into nuclear structure and 3D genome organization will deepen our understanding of the mechanisms governing cell fate determination. [BMB Reports 2024; 57(9): 381-387].

Immunotherapy represents a promising treatment strategy for targeting various tumor types. However, the overall response rate is low due to the tumor microenvironment (TME). In the TME, numerous distinct factors actively induce immunosuppression, restricting the efficacy of anticancer immune reactions. Recently, metabolic reprogramming of tumors has been recognized for its role in modulating the tumor microenvironment to enhance immune cell responses in the TME. Furthermore, recent elucidations underscore the critical role of metabolic limitations imposed by the tumor microenvironment on the effectiveness of antitumor immune cells, guiding the development of novel immunotherapeutic approaches. Hence, achieving a comprehensive understanding of the metabolic requirements of both cancer and immune cells within the TME is pivotal. This insight not only aids in acknowledging the current limitations of clinical practices but also significantly shapes the trajectory of future research endeavors in the domain of cancer immunotherapy. In addition, therapeutic interventions targeting metabolic limitations have exhibited promising potential as combinatory treatments across diverse cancer types. In this review, we first discuss the metabolic barriers in the TME. Second, we explore how the immune response is regulated by metabolites. Finally, we will review the current strategy for targeting metabolism to not simply inhibit tumor growth but also enhance antitumor immune responses. Thus, we could suggest potent combination therapy for improving immunotherapy with metabolic inhibitors. [BMB Reports 2024; 57(9): 388-399].

Glucose-dependent insulinotropic polypeptide (GIP), a 42-aminoacid hormone, exerts multifaceted effects in physiology, most notably in metabolism, obesity, and inflammation. Its significance extends to neuroprotection, promoting neuronal proliferation, maintaining physiological homeostasis, and inhibiting cell death, all of which play a crucial role in the context of neurodegenerative diseases. Through intricate signaling pathways involving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis and regulates a defense system against ferroptosis, an essential process in aging. Our study, utilizing GIP-overexpressing mice and in vitro cell model, elucidates the pivotal role of GIP in preserving neuronal integrity and combating age-related damage, primarily through the Epac/Rap1 pathway. These findings shed light on the potential of GIP as a therapeutic target for the pathogenesis of ferroptosis in neurodegenerative diseases and aging. [BMB Reports 2024; 57(9): 417-423].

Antigen 43 (Ag43) proteins, found on the outer membrane of Escherichia coli, are β-sheets that fold into a unique cylindrical structure known as a β-barrel. There are several known structural similarities between bacterial Ag43 autotransporters and physical components; however, the factors that stabilize the barrel and the mechanism for Ag43 passenger domainmediated translocation across the pore of the β-barrel remain unclear. In this study, we analyzed Ag43β-enhanced green fluorescent protein chimeric variants to provide new insights into the autotransporter Ag43β-barrel assembly, focusing on the impact of the α-helical linker domain. Among the chimeric variants, Ag43β700 showed the highest surface display, which was confirmed through extracellular protease digestion, flow cytometry, and an evaluation of outer membrane vesicles (OMVs). The Ag43β700 module offered reliable information on stable barrel folding and chimera expression at the exterior of the OMVs. [BMB Reports 2024; 57(8): 369-374].

Angiopoietin-like 4 (ANGPTL4) has been identified as an adipokine involved in several non-metabolic and metabolic diseases, including angiogenesis, glucose homeostasis, and lipid metabolism. To date, the role of ANGPTL4 in cancer growth and progression, and metastasis, has been variable. Accumulating evidence suggests that proteolytic processing and posttranslational modifications of ANGPTL4 can significantly alter its function, and may contribute to the multiple and conflicting roles of ANGPTL4 in a tissue-dependent manner. With the growing interest in ANGPTL4 in cancer diagnosis and therapy, we aim to provide an up-to-date review of the implications of ANGPTL4 as a biomarker/oncogene in cancer metabolism, metastasis, and the tumor microenvironment (TME). In cancer cells, ANGPTL4 plays an important role in regulating metabolism by altering intracellular glucose, lipid, and amino acid metabolism. We also highlight the knowledge gaps and future prospect of ANGPTL4 in lymphatic metastasis and perineural invasion through various signaling pathways, underscoring its importance in cancer progression and prognosis. Through this review, a better understanding of the role of ANGPTL4 in cancer progression within the TME will provide new insights into other aspects of tumorigenesis and the potential therapeutic value of ANGPTL4. [BMB Reports 2024; 57(8): 343-351].

Early proatherogenic inflammation constitutes a significant risk factor for atherogenesis development. Despite this, the precise molecular mechanisms driving this pathological progression largely remain elusive. Our study unveils a pivotal role for the microRNA miR-328-5p in dampening endothelial inflammation by modulating the stability of JUNB (JunB proto-oncogene). Perturbation of miR-328-5p levels results in heightened monocyte adhesion to endothelial cells and enhanced transendothelial migration, while its overexpression mitigates these inflammatory processes. Furthermore, miR-328-5p hinders macrophage polarization toward the pro-inflammatory M1 phenotype, and exerts a negative influence on atherosclerotic plaque formation in vivo. By pinpointing JUNB as a direct miR-328-5p target, our research underscores the potential of miR-328-5p as a therapeutic target for inflammatory atherosclerosis. Reintroduction of JUNB effectively counteracts the anti-atherosclerotic effects of miR-328-5p, highlighting the promise of pharmacological miR-328-5p targeting in managing inflammatory atherosclerosis. [BMB Reports 2024; 57(8): 375-380].