Journal of molecular medicine (Berlin, Germany)最新文献

{"title":"Correction to: LncRNA GATA3‑AS1 promoted invasion and migration in human endometrial carcinoma by regulating the miR‑361/ARRB2 axis.","authors":"Yu-Xi Liu, Shuo Yuan, Xiao-Jing Liu, Yan-Xi Huang, Pin Qiu, Jie Gao, Gao-Pi Deng","doi":"10.1007/s00109-022-02259-3","DOIUrl":"https://doi.org/10.1007/s00109-022-02259-3","url":null,"abstract":"","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":" ","pages":"1671"},"PeriodicalIF":4.7,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40559182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone modification in podocyte injury of diabetic nephropathy.","authors":"Simeng Wang,&nbsp;Xinyu Zhang,&nbsp;Qinglian Wang,&nbsp;Rong Wang","doi":"10.1007/s00109-022-02247-7","DOIUrl":"https://doi.org/10.1007/s00109-022-02247-7","url":null,"abstract":"<p><p>Diabetic nephropathy (DN), an important complication of diabetic microvascular disease, is one of the leading causes of end-stage renal disease (ESRD), which brings heavy burdens to the whole society. Podocytes are terminally differentiated glomerular cells, which act as a pivotal component of glomerular filtration barrier. When podocytes are injured, glomerular filtration barrier is damaged, and proteinuria would occur. Dysfunction of podocytes contributes to DN. And degrees of podocyte injury influence prognosis of DN. Growing evidences have shown that epigenetics does a lot in the evolvement of podocyte injury. Epigenetics includes DNA methylation, histone modification, and non-coding RNA. Among them, histone modification plays an indelible role. Histone modification includes histone methylation, histone acetylation, and other modifications such as histone phosphorylation, histone ubiquitination, histone ADP-ribosylation, histone crotonylation, and histone β-hydroxybutyrylation. It can affect chromatin structure and regulate gene transcription to exert its function. This review is to summarize documents about pathogenesis of podocyte injury, most importantly, histone modification of podocyte injury in DN recently to provide new ideas for further molecular research, diagnosis, and treatment.</p>","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":" ","pages":"1373-1386"},"PeriodicalIF":4.7,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33447512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adhesion G protein-coupled receptor gluing action guides tissue development and disease.","authors":"Abhijit Sreepada,&nbsp;Mansi Tiwari,&nbsp;Kasturi Pal","doi":"10.1007/s00109-022-02240-0","DOIUrl":"https://doi.org/10.1007/s00109-022-02240-0","url":null,"abstract":"<p><p>Phylogenetic analysis of human G protein-coupled receptors (GPCRs) divides these transmembrane signaling proteins into five groups: glutamate, rhodopsin, adhesion, frizzled, and secretin families, commonly abbreviated as the GRAFS classification system. The adhesion GPCR (aGPCR) sub-family comprises 33 different receptors in humans. Majority of the aGPCRs are orphan receptors with unknown ligands, structures, and tissue expression profiles. They have a long N-terminal extracellular domain (ECD) with several adhesion sites similar to integrin receptors. Many aGPCRs undergo autoproteolysis at the GPCR proteolysis site (GPS), enclosed within the larger GPCR autoproteolysis inducing (GAIN) domain. Recent breakthroughs in aGPCR research have created new paradigms for understanding their roles in organogenesis. They play crucial roles in multiple aspects of organ development through cell signaling, intercellular adhesion, and cell-matrix associations. They are involved in essential physiological processes like regulation of cell polarity, mitotic spindle orientation, cell adhesion, and migration. Multiple aGPCRs have been associated with the development of the brain, musculoskeletal system, kidneys, cardiovascular system, hormone secretion, and regulation of immune functions. Since aGPCRs have crucial roles in tissue patterning and organogenesis, mutations in these receptors are often associated with diseases with loss of tissue integrity. Thus, aGPCRs include a group of enigmatic receptors with untapped potential for elucidating novel signaling pathways leading to drug discovery. We summarized the current knowledge on how aGPCRs play critical roles in organ development and discussed how aGPCR mutations/genetic variants cause diseases.</p>","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":" ","pages":"1355-1372"},"PeriodicalIF":4.7,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40711265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress induces major depressive disorder by a neutral sphingomyelinase 2-mediated accumulation of ceramide-enriched exosomes in the blood plasma.","authors":"Fabian Schumacher,&nbsp;Alexander Carpinteiro,&nbsp;Michael J Edwards,&nbsp;Gregory C Wilson,&nbsp;Simone Keitsch,&nbsp;Matthias Soddemann,&nbsp;Barbara Wilker,&nbsp;Burkhard Kleuser,&nbsp;Katrin Anne Becker,&nbsp;Christian P Müller,&nbsp;Johannes Kornhuber,&nbsp;Erich Gulbins","doi":"10.1007/s00109-022-02250-y","DOIUrl":"https://doi.org/10.1007/s00109-022-02250-y","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a very common, severe disease with a lifetime prevalence of ~ 10%. The pathogenesis of MDD is unknown and, unfortunately, therapy is often insufficient. We have previously reported that ceramide levels are increased in the blood plasma of patients with MDD and in mice with experimental MDD. Here, we demonstrate that ceramide-enriched exosomes in the blood plasma are increased in mice with stress-induced MDD. Genetic studies reveal that neutral sphingomyelinase 2 is required for the formation of ceramide-enriched exosomes in the blood plasma. Accordingly, induced deficiency of neutral sphingomyelinase 2 prevented mice from the development of stress-induced MDD. Intravenous injection of microparticles from mice with MDD or injection of ceramide-loaded exosomes induced MDD-like behavior in untreated mice, which was abrogated by ex vivo pre-incubation of purified exosomes with anti-ceramide antibodies or ceramidase. Mechanistically, injection of exosomes from mice with MDD or injection of ex vivo ceramide-loaded microparticles inhibited phospholipase D (PLD) in endothelial cells in vitro and in the hippocampus in vivo and thereby decreased phosphatidic acid in the hippocampus, which has been previously shown to mediate MDD by plasma ceramide. In summary, our data indicate that ceramide-enriched exosomes are released by neutral sphingomyelinase 2 into the blood plasma upon stress and mediate stress-induced MDD. KEY MESSAGES: Stress induces ceramide-enriched exosomes in the blood plasma. Ceramide-enriched exosomes mediate major depressive disorder (MDD). Deficiency of neutral sphingomyelinase 2 protects from stress-induced MDD. Neutralization or digestion of ceramide in exosomes prevents stress-induced MDD. Ceramide-enriched exosomes inhibit endothelial phospholipase D in the hippocampus.</p>","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":" ","pages":"1493-1508"},"PeriodicalIF":4.7,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9470690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40335227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: LncRNA GATA3‑AS1 promoted invasion and migration in human endometrial carcinoma by regulating the miR‑361/ARRB2 axis.","authors":"Yu-Xi Liu,&nbsp;Shuo Yuan,&nbsp;Xiao-Jing Liu,&nbsp;Yan-Xi Huang,&nbsp;Pin Qiu,&nbsp;Jie Gao,&nbsp;Gao-Pi Deng","doi":"10.1007/s00109-022-02246-8","DOIUrl":"https://doi.org/10.1007/s00109-022-02246-8","url":null,"abstract":"","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":" ","pages":"1509"},"PeriodicalIF":4.7,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40639791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β1/Smad3 upregulates UCA1 to promote liver fibrosis through DKK1 and miR18a.","authors":"Zhangshuo Yang,&nbsp;Hao Zhang,&nbsp;Maohui Yin,&nbsp;Zhixiang Cheng,&nbsp;Ping Jiang,&nbsp;Maohui Feng,&nbsp;Zhisu Liu,&nbsp;Bo Liao","doi":"10.1007/s00109-022-02248-6","DOIUrl":"https://doi.org/10.1007/s00109-022-02248-6","url":null,"abstract":"<p><p>TGF-β1 is the strongest cytokine known to promote liver fibrosis. It has been previously demonstrated that the activation of TGF-β1 initiates a temporary collagen accumulation program, which is important for wound repair in several organs. Furthermore, temporary extracellular matrix enhancement often leads to progressive fibrosis, which is accountable for cases of severe morbidity and mortality worldwide. However, its action mechanism has not been fully explored. It was previously reported that UCA1 could promote its occurrence and development in various tumors. Importantly, it was reported that TGF-β1 could activate the expression of UCA1 in liver cancer, gastric cancer, and breast cancer. However, the role of UCA1 in organ fibrosis, including liver fibrosis, remains unreported. The present study reported for the first time that TGF-β1/Smad3 could promote liver fibrosis by upregulating UCA1, which further affected DKK1 and collagen, such as COL1A1, COL1A2, and COL3A1. Meanwhile, UCA1 could competitively bind with miR18a to stabilize Smad3 to constitute a positive feedback pathway, which played a significant role in the promotion of liver fibrosis. Altogether, the present study provides a theoretical basis for devising promising treatment strategies for liver fibrosis. KEY MESSAGES : UCA1 was found to promote the progression of liver fibrosis in vitro. UCA1 is regulated by TGF-β1 and promotes liver fibrosis through the canonical Smad pathway. UCA1 can competitively bind with miR18a, promote liver fibrosis by stabilizing Smad3, and form a UCA1-miR18a/Smad3 positive feedback. UCA1 binds EZH2 to inhibit the DKK1 expression and promote liver fibrosis.</p>","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":" ","pages":"1465-1478"},"PeriodicalIF":4.7,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40422106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase separation in immune regulation and immune-related diseases.","authors":"Ning Huang,&nbsp;Hao Dong,&nbsp;Bin Shao","doi":"10.1007/s00109-022-02253-9","DOIUrl":"https://doi.org/10.1007/s00109-022-02253-9","url":null,"abstract":"<p><p>Phase separation is an emerging paradigm for understanding the biochemical interactions between proteins, DNA, and RNA. Research over the past decade has provided mounting evidence that phase separation modulates a great variety of cellular activities. Particularly, phase separation is directly relevant to immune signaling, immune cells, and immune-related diseases like cancer, neurodegenerative diseases, and even SARS-CoV-2. In this review, we summarized current knowledge of phase separation in immunology and emerging findings related to immune responses as they enable possible treatment approaches.</p>","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":" ","pages":"1427-1440"},"PeriodicalIF":4.7,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9462646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33460752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic social stress disrupts the intracellular redistribution of brain hexokinase 3 induced by shifts in peripheral glucose levels.","authors":"Michael A van der Kooij,&nbsp;Liliana Rojas-Charry,&nbsp;Maryam Givehchi,&nbsp;Christina Wolf,&nbsp;Diones Bueno,&nbsp;Sabine Arndt,&nbsp;Stefan Tenzer,&nbsp;Lorenzo Mattioni,&nbsp;Giulia Treccani,&nbsp;Annika Hasch,&nbsp;Michael J Schmeisser,&nbsp;Caterina Vianello,&nbsp;Marta Giacomello,&nbsp;Axel Methner","doi":"10.1007/s00109-022-02235-x","DOIUrl":"https://doi.org/10.1007/s00109-022-02235-x","url":null,"abstract":"<p><p>Chronic stress has the potential to impair health and may increase the vulnerability for psychiatric disorders. Emerging evidence suggests that specific neurometabolic dysfunctions play a role herein. In mice, chronic social defeat (CSD) stress reduces cerebral glucose uptake despite hyperglycemia. We hypothesized that this metabolic decoupling would be reflected by changes in contact sites between mitochondria and the endoplasmic reticulum, important intracellular nutrient sensors, and signaling hubs. We thus analyzed the proteome of their biochemical counterparts, mitochondria-associated membranes (MAMs) from whole brain tissue obtained from CSD and control mice. This revealed a lack of the glucose-metabolizing enzyme hexokinase 3 (HK3) in MAMs from CSD mice. In controls, HK3 protein abundance in MAMs and also in striatal synaptosomes correlated positively with peripheral blood glucose levels, but this connection was lost in CSD. We conclude that the ability of HK3 to traffic to sites of need, such as MAMs or synapses, is abolished upon CSD and surmise that this contributes to a cellular dysfunction instigated by chronic stress. KEY MESSAGES : Chronic social defeat (CSD) alters brain glucose metabolism CSD depletes hexokinase 3 (HK3) from mitochondria-associated membranes (MAMs) CSD results in loss of positive correlation between blood glucose and HK3 in MAMs and synaptosomes.</p>","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":" ","pages":"1441-1453"},"PeriodicalIF":4.7,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9470722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40682150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA GATA3-AS1 promoted invasion and migration in human endometrial carcinoma by regulating the miR-361/ARRB2 axis.","authors":"Yu-Xi Liu,&nbsp;Shuo Yuan,&nbsp;Xiao-Jing Liu,&nbsp;Yan-Xi Huang,&nbsp;Pin Qiu,&nbsp;Jie Gao,&nbsp;Gao-Pi Deng","doi":"10.1007/s00109-022-02222-2","DOIUrl":"https://doi.org/10.1007/s00109-022-02222-2","url":null,"abstract":"<p><p>Endometrial carcinoma (EC) is a kind of fatal female malignancy. lncRNA GATA3-AS1 has been identified as an oncogene in various cancers. However, the functions and mechanisms of GATA3-AS1 in EC remain to be explored. Human EC tissues and four EC cell lines were used. Western blotting and quantitative real-time PCR (qRT-PCR) were used to evaluate the expression of GATA3-AS1, miR-361, and ARRB2. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction among GATA3-AS1, miR-361, and ARRB2. Flow cytometry, colony formation assay, scratch assay, and transwell assay were used to examine the cell apoptosis, proliferation, migration, and invasion of EC cells, respectively. In vivo tumor growth was monitored in nude mice. GATA3-AS1 and ARRB2 were upregulated while miR-361 was downregulated in human EC tissues and EC cells. GATA3-AS1 knockdown constrained cell proliferation, invasion, migration, and EMT while promoting the apoptosis of EC cells by upregulating miR-361. GATA3-AS1 negatively regulated miR-361 expression. ARRB2 was the direct target of miR-361 and could activate the Src/Akt pathway. In vivo, GATA3-AS1 knockdown suppressed tumor progression by upregulating the miR-361 expression. lncRNA GATA3-AS1 promoted EC invasion and migration by the miR-361/ARRB2 axis, which indicated that GATA3-AS1 might be a promising therapeutic option for advanced EC progression. KEY MESSAGES: GATA3-AS1 knockdown suppressed EC proliferation, invasion, and migration. GATA3-AS1 directly inhibited miR-361 as a ceRNA. MiR-361 knockdown reversed the tumor suppressive effect caused by GATA3-AS1 knockdown. MiR-361 bound to ARRB2 directly and suppressed its expression. The GATA3-AS1/miR-361/ARRB2 axis regulated EC cell proliferation, invasion, and migration.</p>","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":" ","pages":"1271-1286"},"PeriodicalIF":4.7,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40561565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mTOR-FABP4 signal is activated in brain arteriovenous malformations in humans.","authors":"Debin Yan,&nbsp;Qiang Hao,&nbsp;Yu Chen,&nbsp;Zhipeng Li,&nbsp;Haibin Zhang,&nbsp;Kexin Yuan,&nbsp;Runting Li,&nbsp;Ruinan Li,&nbsp;Yahui Zhao,&nbsp;Ke Wang,&nbsp;Hao Peng,&nbsp;Dong Zhang,&nbsp;Xiaolin Chen,&nbsp;Yuanli Zhao","doi":"10.1007/s00109-022-02237-9","DOIUrl":"https://doi.org/10.1007/s00109-022-02237-9","url":null,"abstract":"<p><p>Arteriovenous malformations (AVMs) are the most common types of cerebral vascular malformations, which are dynamic lesions with de novo growth potentials. The dysfunction of endothelial cells has been postulated to play a role in the pathogenesis of brain AVMs. mTOR-FABP4 signal enhances the angiogenic responses of endothelial cells and is not activated in the normal cerebral vasculature. Herein, we investigated the hypothesis that the mTOR-FABP4 signal may be activated in brain AVMs. The abundance of molecules in mTOR-FABP4 signal expression was detected by immunohistochemistry and Western blotting; special expressing cells were further characterized by double immunofluorescence using antibodies against various cell-specific markers. Next, several functional assays were performed to analyze the influence of the mTOR-FABP4 signal on proliferation, apoptosis, migration, and vascular tube formation of endothelial cells in human umbilical vein endothelial cells (HUVECs) using rapamycin and L-leucine. The expression of mTOR, p-mTOR, and FABP4 was increased in endothelial cells of human brain AVMs. Endothelial cell mTOR and p-mTOR expression were present in 70% and 55% of brain AVMs, respectively. Moreover, a population of FABP4-positive endothelial cells was detected in 80% of brain AVMs. The mTOR-FABP4 signal was activated and inhibited by L-leucine and rapamycin in HUVECs. The proliferation, apoptosis, migration, and vascular tube formation of endothelial cells could be inhibited by rapamycin. The mTOR-FABP4 signal was activated in human brain AVMs, and the mTOR-FABP4 signal was involved in proliferation, apoptosis, migration, and the vascular tube formation of endothelial cells. Taken together, whether rapamycin has therapeutic potential for treating human brain AVMs is worthy of further study. KEY MESSAGES : We confirmed that the mTOR- FABP4 pathway is activated in human brain arteriovenous malformations. We confirmed that mTOR signaling pathway affects endothelial cell function by regulating proliferation, migration, apoptosis, and tube formation of endothelial cell. Our study can provide theoretical support for mTOR pathway inhibitors in the treatment of human brain arteriovenous malformations.</p>","PeriodicalId":520678,"journal":{"name":"Journal of molecular medicine (Berlin, Germany)","volume":" ","pages":"1287-1297"},"PeriodicalIF":4.7,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40623928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}