BMB Reports最新文献

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].

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].

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].

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].

Parkinson's disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra, is caused by various genetic and environmental factors. Current treatment methods are medication and surgery; however, a primary therapy has not yet been proposed. In this study, we aimed to develop a new treatment for PD that induces direct reprogramming of dopaminergic neurons (iDAN). Achaete-scute family bHLH transcription factor 1 (ASCL1) is a primary factor that initiates and regulates central nervous system development and induces neurogenesis. In addition, it interacts with BRN2 and MYT1L, which are crucial transcription factors for the direct conversion of fibroblasts into neurons. Overexpression of ASCL1 along with the transcription factors NURR1 and LMX1A can directly reprogram iDANs. Using a retrovirus, GFP-tagged ASCL1 was overexpressed in astrocytes. One week of culture in iDAN convertsion medium reprogrammed the astrocytes into iDANs. After 7 days of differentiation, TH+/TUJ1+ cells emerged. After 2 weeks, the number of mature TH+/TUJ1+ dopaminergic neurons increased. Only ventral midbrain (VM) astrocytes exhibited these results, not cortical astrocytes. Thus, VM astrocytes can undergo direct iDAN reprogramming with ASCL1 alone, in the absence of transcription factors that stimulate dopaminergic neurons development. [BMB Reports 2024; 57(8): 363-368].

Hematopoietic stem cell transplantation (HSCT) remains an indispensable therapeutic strategy for various hematological diseases. This review discusses the pivotal role of bone marrow (BM) niches in influencing the efficacy of HSCT and evaluates the current animal models, emphasizing their limitations and the need for alternative models. Traditional animal models, mainly murine xenograft, have provided significant insights, but due to species-specific differences, are often constrained from accurately mimicking human physiological responses. These limitations highlight the importance of developing alternative models that can more realistically replicate human hematopoiesis. Emerging models that include BM organoids and BM-on-a-chip microfluidic systems promise enhanced understanding of HSCT dynamics. These models aim to provide more accurate simulations of the human BM microenvironment, potentially leading to improved preclinical assessments and therapeutic outcomes. This review highlights the complexities of the BM niche, discusses the limitations of current models, and suggests directions for future research using advanced model systems. [BMB Reports 2024; 57(8): 352-362].

Lung cancer is one of the most significant malignancies, with both high morbidity and mortality. CDK10 is closely related to cancer progression and metastasis. However, its role in lung cancer radioresistance demands further clarification. In this study, we demonstrated that CDK10 was downregulated in lung cancer tissues, and CDK10 expression level was associated with the clinical prognosis in lung cancer patients. We also found that silencing CDK10 promoted lung cancer cell proliferation, migration, and radioresistance. We further verified that silencing CDK10 facilitated the activation of JNK/c-Jun signaling, and c-Jun depletion could reverse the effects of CDK10 knockdown in lung cancer cells. Our findings revealed that CDK10 plays an important role in cell growth and radioresistance by inhibiting JNK/c-Jun signaling pathway in lung cancer. Therefore, CDK10 might be a promising therapeutic target in lung cancer. [BMB Reports 2024; 57(7): 336-341].

Arginine methylation, which is catalyzed by protein arginine methyltransferases (Prmts), is known to play a key role in various biological processes. However, the function of Prmts in osteogenic differentiation of mesenchymal stem cells (MSCs) has not been clearly understood. In the current study, we attempted to elucidate a positive role of Prmt7 in osteogenic differentiation. Prmt7-depleted C3H/10T1/2 cells or bone marrow mesenchymal stem cells (BMSCs) showed the attenuated expression of osteogenic specific genes and Alizarin red staining compared to the wild-type cells. Furthermore, we found that Prmt7 deficiency reduced the activation of bone morphogenetic protein (BMP) signaling cascade, which is essential for the regulation of cell fate commitment and osteogenesis. Taken together, our data indicate that Prmt7 plays important regulatory roles in osteogenic differentiation. [BMB Reports 2024; 57(7): 330-335].

[Erratum to: BMB Reports 2024; 57(3): 149-154, PMID: 37817436, PMCID: PMC10979347] The BMB Reports would like to correct in BMB Rep. 57(3):149-154, titled "Stomach clusterin as a gut-derived feeding regulator". This research was supported by the Creative-Pioneering Researchers Program through Seoul National University. Since grant name and number are incorrect, this information has now been corrected as follows: This work was supported by the National Research Foundation of Korea funded by the Korean government (2020R1A2C3004843, 2022M3E5E8017213 to M-S.K., 2020R1C1C10 08033 to O.K.) and by Creative-Pioneering Researchers Program through Seoul National University (to O.K.). The authors apologize for any inconvenience or confusion that may be caused by this error. The ACKNOWLEDGEMENTS of Original PDF version have been corrected.

The aim of the present study is to provide a rational background for silencing the V-set and transmembrane domain containing 2 like (VSTM2L) in consort with recognising soluble VSTM2L against cholangiocarcinoma. A therapeutic target against cholangiocarcinoma was selected using iterative patient partitioning (IPP) calculation, and it was verified by in vitro and in silico analyses. VSTM2L was selected as a potential therapeutic target against cholangiocarcinoma. Silencing the VSTM2L expression significantly attenuated the viability and survival of cholangiocarcinoma cells through blockade of the intracellular signalling pathway. In silico analysis showed that VSTM2L affected the positive regulation of cell growth in cholangiocarcinoma. Liptak's z value revealed that the expression of VSTM2L worsened the prognosis of cholangiocarcinoma patients. In addition, soluble VSTM2L was significantly detected in the whole blood of cholangiocarcinoma patients compared with that of healthy donors. Our report reveals that VSTM2L might be the potential therapeutic target and a soluble prognostic biomarker against cholangiocarcinoma. [BMB Reports 2024; 57(7): 324-329].