BioFactors最新文献

{"title":"Mitigation of experimental ER stress and diabetes mellitus induced peripheral neuropathy by autophagy promoter, 6-BIO","authors":"Praveen Jaiswar,&nbsp;Mitali Bhate,&nbsp;Avadhesha Surolia","doi":"10.1002/biof.2088","DOIUrl":"10.1002/biof.2088","url":null,"abstract":"<p>Neuropathy occurs due to damage to the peripheral/central nervous system either due to injury, disease, or drug usage. Increased endoplasmic reticulum (ER) stress is observed in neuropathy. ER stress also leads to a block in autophagy amplifying neuropathic pain. 6-Bromoindirubin-3′-oxime (6-BIO) is an inhibitor of GSK-3β which suppresses mTOR activity thereby increasing autophagy. Tunicamycin (TM)-mediated ER stress and diabetic rat models were used to elucidate the role of ER stress and autophagy in mitigation of neuropathic pain by 6-BIO. Pain was assessed by behavioral studies in ER stressed/diabetic rats having neuropathy. Western blotting, RT-PCR, and fluorescence microscopy were used to assess the level of autophagy and ER stress after TM and 6-BIO treatment in SH-SY5Y neurons. Intraplantar injection of TM in rats led to peripheral neuropathy which was reduced upon 6-BIO injection. 6-BIO also reduced pain in animals exhibiting diabetic peripheral neuropathy. Modulation in the markers of autophagy (p-mTOR, LC-3, and SQSTM1/p62) shows that 6-BIO induces autophagolysosome formation post TM treatment. Concomitantly, 6-BIO reduces ER stress and c-Fos expression—a neuronal activity and pain marker. Alleviation of pain by the inhibition of ER stress and increased formation of autolysosomes by 6-BIO can be harnessed for treating peripheral neuropathy.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential protein expression and metabolite profiling in glaucoma: Insights from a multi-omics analysis","authors":"Jeong-hun Mok,&nbsp;Do Young Park,&nbsp;Jong Chul Han","doi":"10.1002/biof.2079","DOIUrl":"10.1002/biof.2079","url":null,"abstract":"<p>Various substances within the aqueous humor (AH) can directly or indirectly impact intraocular tissues associated with intraocular pressure (IOP), a critical factor in glaucoma development. This study aims to investigate individual changes in these AH substances and the interactions among altered components through a multi-omics approach. LC/MS analysis was conducted on AH samples from patients with exfoliation syndrome (XFS, <i>n</i> = 5), exfoliation glaucoma (XFG, <i>n</i> = 4), primary open-angle glaucoma (POAG, <i>n</i> = 11), and cataracts (control group, <i>n</i> = 7). Subsequently, differentially expressed proteins and metabolites among groups, alterations in their network interactions, and their biological functions were examined. Both data-independent acquisition and data-dependent acquisition methods were employed to analyze the AH proteome and metabolome, and the results were integrated for a comprehensive analysis. In the proteomics analysis, proteins upregulated in both the XFG and POAG groups were associated with lipid metabolism, complement activation, and extracellular matrix regulation. Metabolomic analysis highlighted significant changes in amino acids related to antioxidant processes in the glaucoma groups. Notably, VTN, APOA1, C6, and L-phenylalanine exhibited significant alterations in the glaucoma groups. Integration of individual omics analyses demonstrated that substances associated with inflammation and lipid metabolism, altered in the glaucoma groups, showed robust interactions within a complex network involving PLG, APOA1, and L-phenylalanine or C3, APOD, and L-valine. These findings offer valuable insights into the molecular mechanisms governing IOP regulation and may contribute to the development of new biomarkers for managing glaucoma.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 6","pages":"1220-1235"},"PeriodicalIF":5.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of the TRHDE-AS1/hsa-miR-449a/ADAMTS5 axis as a novel prognostic biomarker in prostate cancer","authors":"Xin Lian,&nbsp;Honglan Zhou,&nbsp;Si Liu","doi":"10.1002/biof.2083","DOIUrl":"10.1002/biof.2083","url":null,"abstract":"<p>Despite advancements in cancer research, the prognostic implications of competing endogenous RNA (ceRNA) networks in prostate cancer (PCa) remain incompletely understood. This study aimed to elucidate the prognostic relevance of ceRNA networks in PCa, utilizing a comprehensive bioinformatics approach alongside experimental validation. After searching The Cancer Genome Atlas (TCGA) database, RNA sequencing (RNA-Seq) data were extracted to identify differentially expressed RNAs (DERs) between 491 PCa samples and 51 normal prostate tissues, following which a comprehensive bioinformatics strategy was implemented to construct a ceRNA network. An optimal prognostic signature comprising these DERs was then established and validated using TCGA data. In addition, functional validation was performed through RNA pull-down, dual-luciferase reporter assays, quantitative real-time PCR, and western blot analysis conducted in PC-3 and DU145 cell lines, thereby complementing the bioinformatics analysis. A total of 613 DERs, comprising 103 long noncoding RNAs (lncRNAs), 60 microRNAs (miRNAs), and 450 messenger RNAs (mRNAs), were identified and utilized in constructing a ceRNA network, which encompassed 23 lncRNAs, 9 miRNAs, and 52 mRNAs. An optimal prognostic signature was established, including VPS9D1 antisense RNA 1 (VPS9D1-AS1), miR-449a, cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1), targeting protein for Xklp2 (TPX2), solute carrier family 7 member 11 (SLC7A11), copine7 (CPNE7), and maternal embryonic leucine zipper kinase (MELK), yielding area under the curve (AUC) values exceeding 0.8 across training, validation, and entire datasets. Our experiments results revealed an interaction between lncRNA TRHDE antisense RNA 1 (TRHDE-AS1) and miR-449a and that miR-449a could target the ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) mRNA. Knockdown of miR-449a significantly impeded cell proliferation, G1/S transition, migration and invasion, and promoted apoptosis in PC-3 and DU145 cells. Furthermore, knockdown of miR-449a notably downregulated protein expression of CDK4, cyclin D1, N-cadherin and vimentin, while upregulating protein expression of cleaved caspase-3 and E-cadherin. This study contributes to a deeper understanding of the prognostic-linked ceRNA network in PCa, providing fundamental insights that could improve diagnostic and therapeutic approaches for PCa management.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 6","pages":"1251-1267"},"PeriodicalIF":5.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salvia hispanica L. (chia) seed improves redox state and reverts extracellular matrix collagen deposition in skeletal muscle of sucrose-rich diet-fed rats","authors":"Paola G. Illesca,&nbsp;María del R. Ferreira,&nbsp;Adriana Benmelej,&nbsp;María Eugenia D'Alessandro","doi":"10.1002/biof.2087","DOIUrl":"10.1002/biof.2087","url":null,"abstract":"<p>Skeletal muscle (SkM) is a plastic and dynamic tissue, essential in energy metabolism. Growing evidence suggests a close relationship between intramuscular fat accumulation, oxidative stress (OS), extracellular matrix (ECM) remodeling, and metabolic deregulation in SkM. Nowadays natural products emerge as promising alternatives for the treatment of metabolic disorders. We have previously shown that chia seed administration reverts SkM lipotoxicity and whole-body insulin resistant (IR) in sucrose-rich diet (SRD) fed rats. The purpose of the present study was to assess the involvement of OS and fibrosis in SkM metabolic impairment of insulin-resistant rats fed a long-term SRD and the effects of chia seed upon these mechanisms as therapeutic strategy. Results showed that insulin-resistant SRD-fed rats exhibited sarcopenia, increase in lipid peroxidation, altered redox state, and ECM remodeling-increased collagen deposition and lower activity of the metalloproteinase 2 (MMP-2) in SkM. Chia seed increased ferric ion reducing antioxidant power and glutathione reduced form levels, and the activities of glutathione peroxidase and glutathione reductase enzymes. Moreover, chia seed reversed fibrosis and restored the MMP-2 activity. This work reveals a participation of the OS and ECM remodeling in the metabolic alterations of SkM in our experimental model. Moreover, current data show novel properties of chia seed with the potential to attenuate SkM OS and fibrosis, hallmark of insulin-resistant muscle.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk among miR-29, α-SMA, and TGFβ1/β3 in melatonin-induced exosome (Mel-prExo) treated human limbal mesenchymal stem cells (hLMSCs): An insight into scarless healing of the cornea","authors":"Burcugul Altug,&nbsp;Merve Nur Soykan,&nbsp;Sevinc Eyubova,&nbsp;Ayla Eker Sariboyaci,&nbsp;Cezmi Dogan,&nbsp;Onur Ozalp,&nbsp;Eray Atalay","doi":"10.1002/biof.2085","DOIUrl":"10.1002/biof.2085","url":null,"abstract":"<p>Inflammatory mediators that infiltrate the corneal stroma after corneal infections, trauma or refractive surgery can trigger the transformation of corneal keratocytes into myofibroblasts, resulting in highly irregular collagen deposition and subsequently corneal scarring. Mesenchymal stem cells (MSCs) can be used as therapeutic agents to regenerate corneal and conjunctival tissue damage, regulate inflammation, and reduce the development of limbal stem cell failure. The use of MSC-derived exosomes as a cell-free therapeutic vector is a novel therapeutic approach. This study aimed to assess the effect of exosomes obtained from melatonin (Mel)-treated human limbal mesenchymal stem cells (hLMSCs) on naïve hLMSCs and to determine their influence on the antifibrotic and pro-regenerative pathways involved in corneal scarring. hLMSCs were treated with varying concentrations of Mel, followed by isolation and characterization of the procured exosomes (Mel-prExos). These exosomes were added to the cell culture media of naïve hLMSCs to examine their antifibrotic and pro-regenerative effects. The expression of miR-155, miR-29, TGFβ1, TGFβ3, PPARγ, and α-SMA miRNAs and genes were compared between Mel-treated hLMSCs and Mel-prExo-treated hLMSCs by using real-time PCR. We found that at 1 μM Mel and in the presence of Mel-prExos, TGFβ1 was expressed 0.001-fold, while TGFβ3 was expressed 0.6-fold. miR-29 expression was increased 38-fold in the control-Exo group compared to that in the control group. Changes in TGFβ1/β3 and α-SMA expression are associated with miR-29 and miR-155. This approach could prove beneficial for ocular surface tissue engineering applications.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 6","pages":"1287-1297"},"PeriodicalIF":5.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limosilactobacillus reuteri DSM 17938 relieves inflammation, endoplasmic reticulum stress, and autophagy in hippocampus of western diet-fed rats by modulation of systemic inflammation","authors":"Arianna Mazzoli,&nbsp;Maria Stefania Spagnuolo,&nbsp;Francesca De Palma,&nbsp;Natasha Petecca,&nbsp;Angela Di Porzio,&nbsp;Valentina Barrella,&nbsp;Antonio Dario Troise,&nbsp;Rosanna Culurciello,&nbsp;Sabrina De Pascale,&nbsp;Andrea Scaloni,&nbsp;Gianluigi Mauriello,&nbsp;Susanna Iossa,&nbsp;Luisa Cigliano","doi":"10.1002/biof.2082","DOIUrl":"10.1002/biof.2082","url":null,"abstract":"<p>The consumption of western diets, high in fats and sugars, is a crucial contributor to brain molecular alterations, cognitive dysfunction and neurodegenerative diseases. Therefore, a mandatory challenge is the individuation of strategies capable of preventing diet-induced impairment of brain physiology. A promising strategy might consist in the administration of probiotics that are known to influence brain function via the gut-brain axis. In this study, we explored whether <i>Limosilactobacillus reuteri</i> DSM 17938 (<i>L. reuteri</i>)-based approach can counteract diet-induced neuroinflammation, endoplasmic reticulum stress (ERS), and autophagy in hippocampus, an area involved in learning and memory, in rat fed a high fat and fructose diet. The western diet induced a microbiota reshaping, but <i>L. reuteri</i> neither modulated this change, nor the plasma levels of short-chain fatty acids. Interestingly, pro-inflammatory signaling pathway activation (increased NFkB phosphorylation, raised amounts of toll-like receptor-4, tumor necrosis factor-alpha, interleukin-6, GFAP, and Haptoglobin), as well as activation of ERS (increased PERK and eif2α phosphorylation, higher C/EBP-homologous protein amounts) and autophagy (increased beclin, P62-sequestosome-1, and LC3 II) was revealed in hippocampus of western diet fed rats. All these hippocampal alterations were prevented by <i>L. reuteri</i> administration, showing for the first time a neuroprotective role of this specific probiotic strain, mainly attributable to its ability to regulate western diet-induced metabolic endotoxemia and systemic inflammation, as decreased levels of lipopolysaccharide, plasma cytokines, and adipokines were also found. Therapeutic strategies based on the use of <i>L. reuteri</i> DSM17938 could be beneficial in reversing metabolic syndrome-mediated brain dysfunction and cognitive decline.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 6","pages":"1236-1250"},"PeriodicalIF":5.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catechol-induced covalent modifications modulate the aggregation tendency of α-synuclein: An in-solution and in-silico study","authors":"Ilenia Inciardi,&nbsp;Elena Rizzotto,&nbsp;Francesco Gregoris,&nbsp;Benedetta Fongaro,&nbsp;Alice Sosic,&nbsp;Giovanni Minervini,&nbsp;Patrizia Polverino de Laureto","doi":"10.1002/biof.2086","DOIUrl":"10.1002/biof.2086","url":null,"abstract":"<p>Parkinson's disease (PD) stands as a challenging neurodegenerative condition characterized by the emergence of Lewy Bodies (LBs), intracellular inclusions within dopaminergic neurons. These LBs harbor various proteins, prominently including α-Synuclein (Syn) aggregates, implicated in disease pathology. A promising avenue in PD treatment involves targeting Syn aggregation. Recent findings from our research have shown that 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylethanol (DOPET) possess the ability to impede the formation of Syn fibrils by disrupting the aggregation process. Notably, these compounds primarily engage in noncovalent interactions with the protein, leading to the formation of off-pathway oligomers that deter fibril growth. Through proteolysis studies and mass spectrometry (MS) analysis, we have identified potential covalent modifications of Syn in the presence of DOPAC, although the exact site remains elusive. Employing molecular dynamics simulations, we delved into how DOPAC-induced covalent alterations might affect the mechanism of Syn aggregation. Our findings indicate that the addition of a covalent adduct on certain residues enhances fibril flexibility without compromising its secondary structure stability. Furthermore, in the monomeric state, the modified residue fosters novel bonding interactions, thereby influencing long-range interactions between the N- and C-termini of the protein.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear receptor 4A1 (NR4A1) upregulated by n-butylidenephthalide via the mitogen-activated protein kinase (MAPK) pathway ameliorates drug-induced gingival enlargement","authors":"Tomoya Ueda,&nbsp;Shinji Matsuda,&nbsp;Yurika Ninomiya,&nbsp;Fuminori Nakashima,&nbsp;Keisuke Yasuda,&nbsp;Daisuke Furutama,&nbsp;Takumi Memida,&nbsp;Tetsuya Yoshimoto,&nbsp;Mikihito Kajiya,&nbsp;Kouji Ohta,&nbsp;Kazuhisa Ouhara,&nbsp;Noriyoshi Mizuno","doi":"10.1002/biof.2077","DOIUrl":"10.1002/biof.2077","url":null,"abstract":"<p>Drug-induced gingival enlargement (DIGE) is a side effect of ciclosporin, calcium channel blockers, and phenytoin. DIGE is a serious disease that leads to masticatory and esthetic disorders, severe caries, and periodontitis but currently has no standard treatment. We recently reported that nuclear receptor 4A1 (NR4A1) is a potential therapeutic target for DIGE. This study aimed to evaluate the therapeutic effects of <i>n</i>-butylidenephthalide (BP), which increases the expression of NR4A1, on DIGE. In this study, <i>NR4A1</i> mRNA expression was analyzed in the patients with periodontal disease (PD) and DIGE. We evaluated the effect of BP on NR4A1 expression in gingival fibroblasts and in a DIGE mouse model. RNA sequencing (RNA-seq) was conducted to identify the mechanisms by which BP increases NR4A1 expression. The results showed that <i>NR4A1</i> mRNA expression in the patients with DIGE was significantly lower than the patients with PD. BP suppressed the upregulation of <i>COL1A1</i> expression, which was upregulated by TGF-β. BP also ameliorated gingival overgrowth in DIGE mice and reduced <i>Col1a1</i> and <i>Pai1</i> expression. BP also decreased <i>Il1β</i> mRNA expression in gingival tissue in DIGE. RNA-seq results showed an increase in the expression of several genes related to mitogen-activated protein kinase including DUSP genes in gingival fibroblasts stimulated by BP. Treatment with ERK and JNK inhibitors suppressed the BP-induced increase in NR4A1 expression. In addition, BP promoted the phosphorylation of ERK in gingival fibroblasts. In conclusion, BP increases NR4A1 expression in gingival fibroblasts through ERK and JNK signaling, demonstrating its potential as a preventive and therapeutic agent against DIGE.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 6","pages":"1192-1207"},"PeriodicalIF":5.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease","authors":"Muhammad Asim,&nbsp;Huajie Wang,&nbsp;Abdul Waris,&nbsp;Gao Qianqian,&nbsp;Xi Chen","doi":"10.1002/biof.2081","DOIUrl":"10.1002/biof.2081","url":null,"abstract":"<p>Cholecystokinin (CCK) plays a key role in various brain functions, including both health and disease states. Despite the extensive research conducted on CCK, there remain several important questions regarding its specific role in the brain. As a result, the existing body of literature on the subject is complex and sometimes conflicting. The primary objective of this review article is to provide a comprehensive overview of recent advancements in understanding the central nervous system role of CCK, with a specific emphasis on elucidating CCK's mechanisms for neuroplasticity, exploring its interactions with other neurotransmitters, and discussing its significant involvement in neurological disorders. Studies demonstrate that CCK mediates both inhibitory long-term potentiation (iLTP) and excitatory long-term potentiation (eLTP) in the brain. Activation of the GPR173 receptor could facilitate iLTP, while the Cholecystokinin B receptor (CCKBR) facilitates eLTP. CCK receptors' expression on different neurons regulates activity, neurotransmitter release, and plasticity, emphasizing CCK's role in modulating brain function. Furthermore, CCK plays a pivotal role in modulating emotional states, Alzheimer's disease, addiction, schizophrenia, and epileptic conditions. Targeting CCK cell types and circuits holds promise as a therapeutic strategy for alleviating these brain disorders.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 6","pages":"1060-1075"},"PeriodicalIF":5.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiopoietin-like protein 4 induces growth hormone variant secretion and aggravates insulin resistance during pregnancy, linking obesity to gestational diabetes mellitus","authors":"Chun-Heng Kuo,&nbsp;Shu-Huei Wang,&nbsp;Hsien-Chia Juan,&nbsp;Szu-Chi Chen,&nbsp;Ching-Hua Kuo,&nbsp;Han-Chun Kuo,&nbsp;Shin-Yu Lin,&nbsp;Hung-Yuan Li","doi":"10.1002/biof.2076","DOIUrl":"10.1002/biof.2076","url":null,"abstract":"<p>Angiopoietin-like protein 4 (ANGPTL4) is a secretory glycoprotein involved in regulating glucose homeostasis in non-pregnant subjects. However, its role in glucose metabolism during pregnancy and the pathophysiology of gestational diabetes mellitus (GDM) remains elusive. Thus, this study aimed to clarify the relationship between ANGPTL4 and GDM and investigate the pathophysiology of placental ANGPTL4 in glucose metabolism. We investigated this issue using blood and placenta samples in 957 pregnant women, the human 3A-sub-E trophoblast cell line, and the L6 skeletal muscle cell line. We found that ANGPTL4 expression in the placenta was higher in obese pregnant women than in lean controls. Palmitic acid significantly induced ANGPTL4 expression in trophoblast cells in a dose–response manner. ANGPTL4 overexpression in trophoblast cells resulted in endoplasmic reticulum (ER) stress, which stimulated the expression and secretion of growth hormone-variant (GH2) but not human placental lactogen. In L6 skeletal muscle cells, soluble ANGPTL4 suppressed insulin-mediated glucose uptake through the epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinases 1/2 (ERK 1/2) pathways. In pregnant women, plasma ANGPTL4 concentrations in the first trimester predicted the incidence of GDM and were positively associated with BMI, plasma triglyceride, and plasma GH2 in the first trimester. However, they were negatively associated with insulin sensitivity index ISI_0,120 in the second trimester. Overall, placental ANGPTL4 is induced by obesity and is involved in the pathophysiology of GDM via the induction of ER stress and GH2 secretion. Soluble ANGPTL4 can lead to insulin resistance in skeletal muscle cells and is an early biomarker for predicting GDM.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 6","pages":"1176-1191"},"PeriodicalIF":5.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}