Inflammation and Regeneration最新文献

{"title":"A case of refractory systemic lupus erythematosus with monocytosis exhibiting somatic KRAS mutation","authors":"S. Law, S. Akizuki, A. Morinobu, K. Ohmura","doi":"10.1186/s41232-022-00195-w","DOIUrl":"https://doi.org/10.1186/s41232-022-00195-w","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"42 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65781005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Towards a better understanding of the physiology of the lymphatics","authors":"Masayuki Miyasaka","doi":"10.1186/s41232-022-00200-2","DOIUrl":"https://doi.org/10.1186/s41232-022-00200-2","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"42 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65781267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of a BAC transgenic mouse strain that expresses CreERT and a fluorescent protein under the transcriptional control of the Fzd5 locus","authors":"S. Miyagi, Y. Kato, Ayako Watanabe, K. Miyamoto, Rintaro Yoshikawa, K. Hagiya, D. Hirano, Y. Matsuzaki","doi":"10.1186/s41232-022-00194-x","DOIUrl":"https://doi.org/10.1186/s41232-022-00194-x","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48265623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial-specific depletion of TGF-β signaling affects lymphatic function.","authors":"Kunpei Fukasawa,&nbsp;Kako Hanada,&nbsp;Kei Ichikawa,&nbsp;Masanori Hirashima,&nbsp;Takahiro Takagi,&nbsp;Susumu Itoh,&nbsp;Testuro Watabe,&nbsp;Fumiko Itoh","doi":"10.1186/s41232-021-00185-4","DOIUrl":"https://doi.org/10.1186/s41232-021-00185-4","url":null,"abstract":"<p><strong>Background: </strong>Transforming growth factor (TGF)-β is a multifunctional cytokine involved in cell differentiation, cell proliferation, and tissue homeostasis. Although TGF-β signaling is essential for maintaining blood vessel functions, little is known about the role of TGF-β in lymphatic homeostasis.</p><p><strong>Methods: </strong>To delineate the role of TGF-β signaling in lymphatic vessels, TβRII^fl/fl mice were crossed with Prox1-Cre^ERT2 mice to generate TβRII^fl/fl; Prox1-Cre^ERT2 mice. The TβRII gene in the lymphatic endothelial cells (LECs) of the conditional knockout TβRII^iΔLEC mice was selectively deleted using tamoxifen. The effects of TβRII gene deletion on embryonic lymphangiogenesis, postnatal lymphatic structure and drainage function, tumor lymphangiogenesis, and lymphatic tumor metastasis were investigated.</p><p><strong>Results: </strong>Deficiency of LEC-specific TGF-β signaling in embryos, where lymphangiogenesis is active, caused dorsal edema with dilated lymphatic vessels at E13.5. Postnatal mice in which lymphatic vessels had already been formed displayed dilation and increased bifurcator of lymphatic vessels after tamoxifen administration. Similar dilation was also observed in tumor lymphatic vessels. The drainage of FITC-dextran, which was subcutaneously injected into the soles of the feet of the mice, was reduced in TβRII^iΔLEC mice. Furthermore, Lewis lung carcinoma cells constitutively expressing GFP (LLC-GFP) transplanted into the footpads of the mice showed reduced patellar lymph node metastasis.</p><p><strong>Conclusion: </strong>These data suggest that TGF-β signaling in LECs maintains the structure of lymphatic vessels and lymphatic homeostasis, in addition to promoting tumor lymphatic metastasis. Therefore, suppression of TGF-β signaling in LECs might be effective in inhibiting cancer metastasis.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"35"},"PeriodicalIF":8.1,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39768546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-6: evolving role in the management of neuropathic pain in neuroimmunological disorders.","authors":"Kenichi Serizawa,&nbsp;Haruna Tomizawa-Shinohara,&nbsp;Shota Miyake,&nbsp;Kenji Yogo,&nbsp;Yoshihiro Matsumoto","doi":"10.1186/s41232-021-00184-5","DOIUrl":"https://doi.org/10.1186/s41232-021-00184-5","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic pain in neuroimmunological disorders refers to pain caused by a lesion or disease of the somatosensory system such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MS and NMOSD are autoimmune disorders of the central nervous system, and ≥ 50% of patients with these disorders experience chronic neuropathic pain. The currently available medications for the management of neuropathic pain have limited effectiveness in patients with MS and NMOSD, and there is an unmet medical need to identify novel therapies for the management of chronic neuropathic pain in these patients. In this review article, we summarize the role of interleukin-6 (IL-6) in the pathogenesis of MS and NMOSD and the ameliorative effects of anti-IL-6 therapies in mouse models of experimental autoimmune encephalomyelitis (EAE).</p><p><strong>Main body: </strong>Intraperitoneal injection of MR16-1, an anti-IL-6 receptor (IL-6R) antibody, reduced mechanical allodynia and spontaneous pain in EAE mice, which was attributed to a reduction in microglial activation and inhibition of the descending pain inhibitory system. The effect of anti-IL-6 therapies in ameliorating neuropathic pain in the clinical setting is controversial; a reduction in pain intensity has been reported with an anti-IL-6 antibody in four studies, namely a case report, a pilot study, a retrospective observational study, and a case series. Pain intensity was evaluated using a numerical rating scale (NRS), with a lower score indicating lesser pain. A reduction in the NRS score was reported in all four studies. However, in two randomized controlled trials of another anti-IL-6R antibody, the change in the visual analog scale pain score was not statistically significantly different when compared with placebo. This was attributed to the low mean pain score at baseline in both the trials and the concomitant use of medications for pain in one of the trials, which may have masked the effects of the anti-IL-6R antibody on neuropathic pain.</p><p><strong>Conclusion: </strong>Thus, anti-IL-6 therapies might have a potential to reduce neuropathic pain, but further investigations are warranted to clarify the effect of inhibition of IL-6 signaling on neuropathic pain associated with MS and NMOSD.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"34"},"PeriodicalIF":8.1,"publicationDate":"2021-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39581959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain.","authors":"Yuki Yamamura,&nbsp;Yoshimi Kawamura,&nbsp;Yuki Oiwa,&nbsp;Kaori Oka,&nbsp;Nobuyuki Onishi,&nbsp;Hideyuki Saya,&nbsp;Kyoko Miura","doi":"10.1186/s41232-021-00182-7","DOIUrl":"https://doi.org/10.1186/s41232-021-00182-7","url":null,"abstract":"<p><strong>Background: </strong>The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan of more than 37 years and shows a negligible senescence phenotype, suggesting that tissue stem cells of NMRs are highly capable of maintaining homeostasis. However, the properties of NMR tissue stem cells, including neural stem cells (NSCs), are largely unclear.</p><p><strong>Methods: </strong>Neural stem/progenitor cells (NS/PCs) were isolated from the subventricular zone of the neonate NMR brain (NMR-NS/PCs) and cultured in neurosphere and adherent culture conditions. Expression of NSC markers and markers of neurons, astrocytes, and oligodendrocytes was analyzed by immunocytochemistry. In adherent culture conditions, the proliferation rate and cell cycle of NMR-NS/PCs were assessed and compared with those of NS/PCs from mice (mouse-NS/PCs). The DNA damage response to γ-irradiation was analyzed by immunocytochemistry and reverse transcription-quantitative PCR.</p><p><strong>Results: </strong>NMR-NS/PCs expressed several NSC markers and differentiated into neurons, astrocytes, and oligodendrocytes. NMR-NS/PCs proliferated markedly slower than mouse-NS/PCs, and a higher percentage of NMR-NS/PCs than mouse-NS/PCs was in G0/G1 phase. Notably, upon γ-irradiation, NMR-NS/PCs exhibited a faster initiation of the DNA damage response and were less prone to dying than mouse-NS/PCs.</p><p><strong>Conclusions: </strong>NMR-NS/PCs were successfully isolated and cultured. The slow proliferation of NMR-NS/PCs and their resistance to DNA damage may help to prevent stem cell exhaustion in the brain during the long lifespan of NMRs. Our findings provide novel insights into the mechanism underlying delayed aging of NMRs. Further analysis of NMR tissue stem cells may lead to the development of new strategies that can prevent aging in humans.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"31"},"PeriodicalIF":8.1,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39844200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular biology of autoinflammatory diseases.","authors":"Junya Masumoto,&nbsp;Wei Zhou,&nbsp;Shinnosuke Morikawa,&nbsp;Sho Hosokawa,&nbsp;Haruka Taguchi,&nbsp;Toshihiro Yamamoto,&nbsp;Mie Kurata,&nbsp;Naoe Kaneko","doi":"10.1186/s41232-021-00181-8","DOIUrl":"https://doi.org/10.1186/s41232-021-00181-8","url":null,"abstract":"<p><p>The long battle between humans and various physical, chemical, and biological insults that cause cell injury (e.g., products of tissue damage, metabolites, and/or infections) have led to the evolution of various adaptive responses. These responses are triggered by recognition of damage-associated molecular patterns (DAMPs) and/or pathogen-associated molecular patterns (PAMPs), usually by cells of the innate immune system. DAMPs and PAMPs are recognized by pattern recognition receptors (PRRs) expressed by innate immune cells; this recognition triggers inflammation. Autoinflammatory diseases are strongly associated with dysregulation of PRR interactomes, which include inflammasomes, NF-κB-activating signalosomes, type I interferon-inducing signalosomes, and immuno-proteasome; disruptions of regulation of these interactomes leads to inflammasomopathies, relopathies, interferonopathies, and proteasome-associated autoinflammatory syndromes, respectively. In this review, we discuss the currently accepted molecular mechanisms underlying several autoinflammatory diseases.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"33"},"PeriodicalIF":8.1,"publicationDate":"2021-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39506702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A short review on lymphatic endothelial cell heterogeneity.","authors":"Masayuki Miyasaka","doi":"10.1186/s41232-021-00183-6","DOIUrl":"https://doi.org/10.1186/s41232-021-00183-6","url":null,"abstract":"<p><p>Recent single-cell RNA sequencing studies in mouse and human have clearly indicated that lymphatic endothelial cells (LECs) consist of multiple cell subsets, each expressing a unique set of genes, residing in distinct locations in the body. These studies have also revealed a conserved pattern of gene expression in LECs across animal species, as well as specialized sets of genes unique to each species. However, the extent to which this heterogeneity is adaptive to the external milieu surrounding LECs has remained unclear. The transcriptional and regulatory pathways that program the different subsets of LECs also remain unexplored.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"32"},"PeriodicalIF":8.1,"publicationDate":"2021-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39506764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of chaperone-mediated autophagy in the pathophysiology including pulmonary disorders.","authors":"Yusuke Hosaka,&nbsp;Jun Araya,&nbsp;Yu Fujita,&nbsp;Kazuyoshi Kuwano","doi":"10.1186/s41232-021-00180-9","DOIUrl":"https://doi.org/10.1186/s41232-021-00180-9","url":null,"abstract":"<p><p>Autophagy is a highly conserved mechanism of delivering cytoplasmic components for lysosomal degradation. Among the three major autophagic pathways, chaperone-mediated autophagy (CMA) is primarily characterized by its selective nature of protein degradation, which is mediated by heat shock cognate 71 kDa protein (HSC70: also known as HSPA8) recognition of the KFERQ peptide motif in target proteins. Lysosome-associated membrane protein type 2A (LAMP2A) is responsible for substrate binding and internalization to lysosomes, and thus, the lysosomal expression level of LAMP2A is a rate-limiting factor for CMA. Recent advances have uncovered not only physiological but also pathological role of CMA in multiple organs, including neurodegenerative disorders, kidney diseases, liver diseases, heart diseases, and cancers through the accumulation of unwanted proteins or increased degradation of target proteins with concomitant metabolic alterations resulting from CMA malfunction. With respect to pulmonary disorders, the involvement of CMA has been demonstrated in lung cancer and chronic obstructive pulmonary disease (COPD) pathogenesis through regulating apoptosis. Further understanding of CMA machinery may shed light on the molecular mechanisms of refractory disorders and lead to novel treatment modalities through CMA modulation.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"29"},"PeriodicalIF":8.1,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39474029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice.","authors":"Shunsuke Nojiri,&nbsp;Atsunori Tsuchiya,&nbsp;Kazuki Natsui,&nbsp;Suguru Takeuchi,&nbsp;Takayuki Watanabe,&nbsp;Yuichi Kojima,&nbsp;Yusuke Watanabe,&nbsp;Hiroteru Kamimura,&nbsp;Masahiro Ogawa,&nbsp;Satoko Motegi,&nbsp;Takahiro Iwasawa,&nbsp;Takeki Sato,&nbsp;Masaru Kumagai,&nbsp;Yui Ishii,&nbsp;Tomomi Kitayama,&nbsp;Yu-Tung Li,&nbsp;Yuya Ouchi,&nbsp;Takashi Shimbo,&nbsp;Masaaki Takamura,&nbsp;Katsuto Tamai,&nbsp;Shuji Terai","doi":"10.1186/s41232-021-00177-4","DOIUrl":"https://doi.org/10.1186/s41232-021-00177-4","url":null,"abstract":"<p><p>The liver has a high regenerative ability and can induce spontaneous regression of fibrosis when early liver damage occurs; however, these abilities are lost when chronic liver damage results in decompensated cirrhosis. Cell therapies, such as mesenchymal stem cell (MSC) and macrophage therapies, have attracted attention as potential strategies for mitigating liver fibrosis. Here, we evaluated the therapeutic effects of HMGB1 peptide synthesized from box A of high mobility group box 1 protein. Liver damage and fibrosis were evaluated using a carbon tetrachloride (CCl₄)-induced cirrhosis mouse model. The effects of HMGB1 peptide against immune cells were evaluated by single-cell RNA-seq using liver tissues, and those against monocytes/macrophages were further evaluated by in vitro analyses. Administration of HMGB1 peptide did not elicit a rapid response within 36 h, but attenuated liver damage after 1 week and suppressed fibrosis after 2 weeks. Fibrosis regression developed over time, despite continuous liver damage, suggesting that administration of this peptide could induce fibrolysis. In vitro analyses could not confirm a direct effect of HMGB1 peptide against monocyte/macrophages. However, macrophages were the most affected immune cells in the liver, and the number of scar-associated macrophages (Trem2+Cd9+ cells) with anti-inflammatory markers increased in the liver following HMGB1 treatment, suggesting that indirect effects of monocytes/macrophages were important for therapeutic efficacy. Overall, we established a new concept for cell-free therapy using HMGB1 peptide for cirrhosis through the induction of anti-inflammatory macrophages.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"28"},"PeriodicalIF":8.1,"publicationDate":"2021-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39473297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}