Journal of molecular endocrinology最新文献_第8页

Temporal regulation of interferon signalling in human EndoC-βH1 cells. 人EndoC-βH1细胞干扰素信号传导的时间调控。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-05-19 DOI: 10.1530/JME-21-0224

Shalinee Dhayal, Kaiyven Afi Leslie, Mohammad Baity, Pouria Akhbari, Sarah J Richardson, Mark A Russell, Noel G Morgan

{"title":"Temporal regulation of interferon signalling in human EndoC-βH1 cells.","authors":"Shalinee Dhayal, Kaiyven Afi Leslie, Mohammad Baity, Pouria Akhbari, Sarah J Richardson, Mark A Russell, Noel G Morgan","doi":"10.1530/JME-21-0224","DOIUrl":"10.1530/JME-21-0224","url":null,"abstract":"During the development of type 1 diabetes, interferons (IFN) are elaborated from islet-infiltrating immune cells and/or from virally infected β-cells. They act via specific receptors to increase, acutely, the phosphorylation of the transcription factors STAT1 and 2. However, the longer-term impacts of chronic IFN stimulation are poorly understood and were investigated in the current study. Human EndoC-βH1 cells were treated with IFNα, IFNγ or IFNλ either acutely (<2 h) or chronically (≥24 h) and STAT phosphorylation, expression and activity were assessed by Western blotting and transcriptional reporter assays. Exposure of β-cells to IFNα or IFNλ induced a swift increase in the phosphorylation of both STAT1 and STAT2, whereas IFNγ increased only pSTAT1. Over more extended periods (≥24 h), STAT phosphorylation declined but STAT1 and STAT2 expression were enhanced in a sustained manner. All IFNs stimulated ISRE transcriptional activity (but with different time courses), whereas GAS activity was responsive only to IFNγ. The re-addition of a second bolus of IFNα, 24 h after an initial dose, failed to cause renewed STAT1/2 phosphorylation. By contrast, when IFNγ was added 24 h after exposure to IFNα, rapid STAT1 phosphorylation was re-initiated. Exposure of β-cells to IFNs leads to rapid, transient, STAT phosphorylation and to slower and more sustained increases in total STAT1/2 levels. The initial phosphorylation response is accompanied by marked desensitisation to the cognate agonist. Together, the results reveal that the response of β-cells to IFNs is regulated both temporally and quantitatively to achieve effective signal integration.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"69 2","pages":"299-313"},"PeriodicalIF":3.5,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10099516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Genetic bases of pheochromocytoma and paraganglioma. 嗜铬细胞瘤和副神经节瘤的遗传基础。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-05-07 DOI: 10.1530/endoabs.81.s9.1

A. Cascón, Bruna Calsina, María Monteagudo, Sara Mellid, Alberto Díaz-Talavera, M. Currás-Freixes, M. Robledo

{"title":"Genetic bases of pheochromocytoma and paraganglioma.","authors":"A. Cascón, Bruna Calsina, María Monteagudo, Sara Mellid, Alberto Díaz-Talavera, M. Currás-Freixes, M. Robledo","doi":"10.1530/endoabs.81.s9.1","DOIUrl":"https://doi.org/10.1530/endoabs.81.s9.1","url":null,"abstract":"The genetics of pheochromocytoma and paraganglioma (PPGL) has become increasingly complex over the last two decades. The list of genes involved in the development of these tumors has grown steadily, and there are currently more than 20 driver genes implicated in either the hereditary or the sporadic nature of the disease. Although genetic diagnosis is achieved in about 75-80% of patients, the genetic aetiology remains unexplained in a significant percentage of cases. Patients lacking a genetic diagnosis include not only those with apparently sporadic PPGL, but also patients with a family history of the disease or with multiple tumors, that meet the criteria to be considered as candidates for carrying germline mutations in yet undiscovered genes. Mutations in known PPGL genes deregulate three main signaling pathways (hypoxia, kinase signaling and wnt-signaling pathways), which could be the starting point for the development of a personalised treatment for PPGL patients. Furthermore, the integration of results from several genomic high-throughput platforms enables the discovery of regulatory mechanisms that cannot be identified by analyzing each piece of information separately. These strategies are powerful tools for elucidating optimal therapeutic options based on molecular biomarkers in PPGL, and represent an important step towards the achievement of precision medicine for patients with metastatic PPGL.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43824128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

The Chd4 subunit of the NuRD complex regulates Pdx1-controlled genes involved in β-cell function. NuRD复合体的Chd4亚基调节参与β细胞功能的pdx1控制基因。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-05-01 DOI: 10.1530/JME-22-0011

Rebecca K Davidson, Staci A. Weaver, Nolan Casey, Sukrati Kanojia, Elise Hogarth, Rebecca Schneider Aguirre, E. Sims, C. Evans-Molina, Jason M Spaeth

{"title":"The Chd4 subunit of the NuRD complex regulates Pdx1-controlled genes involved in β-cell function.","authors":"Rebecca K Davidson, Staci A. Weaver, Nolan Casey, Sukrati Kanojia, Elise Hogarth, Rebecca Schneider Aguirre, E. Sims, C. Evans-Molina, Jason M Spaeth","doi":"10.1530/JME-22-0011","DOIUrl":"https://doi.org/10.1530/JME-22-0011","url":null,"abstract":"Type 2 diabetes (T2D) is associated with loss of transcription factors (TFs) from a subset of failing β-cells. Among these TFs is Pdx1, which controls the expression of numerous genes involved in maintaining β-cell function and identity. Pdx1 activity is modulated by transcriptional coregulators and has recently been shown, through an unbiased screen, to interact with the Chd4 ATPase subunit of the Nucleosome Remodeling and Deacetylase complex. Chd4 contributes to the maintenance of cellular identity and functional status of numerous different cell types. Here, we demonstrate Pdx1 dynamically interacts with Chd4 under physiological and stimulatory conditions within islet β-cells. We establish a fundamental role for Chd4 in regulating insulin secretion and modulating numerous Pdx1 bound genes in vitro, including the MafA TF, where we discovered Chd4 is bound at the MafA Region 3 enhancer. Furthermore, we found that Pdx1:Chd4 interactions are significantly compromised in islet β-cells under metabolically-induced stress in vivo and in human donor tissues with T2D. Our findings establish a fundamental role for Chd4 in regulating insulin secretion and modulating Pdx1-bound genes in vitro, and disruption of Pdx1:Chd4 interactions coincides with β-cell dysfunction associated with T2D.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43968059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Liraglutide stimulates the β-catenin signaling cascade in mouse epididymal fat tissue. 利拉鲁肽刺激小鼠附睾脂肪组织中的β-连环蛋白信号级联反应。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-05-01 DOI: 10.1530/JME-22-0026

J. Gu, W. Shao, Di Liu, Jiajun Feng, Juan Pang, T. Jin

{"title":"Liraglutide stimulates the β-catenin signaling cascade in mouse epididymal fat tissue.","authors":"J. Gu, W. Shao, Di Liu, Jiajun Feng, Juan Pang, T. Jin","doi":"10.1530/JME-22-0026","DOIUrl":"https://doi.org/10.1530/JME-22-0026","url":null,"abstract":"Although canonical Wnt signaling pathway activation was shown to negatively regulate adipogenesis, recent investigations suggest that Wnt pathway effectors TCF7L2 and β-catenin (β-cat) in adipose tissues are also involved in energy homeostasis during adulthood. In assessing metabolic beneficial effect of GLP-1-based diabetes-drugs in high fat diet (HFD) challenged mice, we observed that liraglutide treatment affected expression of a battery of adipose tissue-specific genes, including that encode adiponectin and leptin, mainly in epididymal white adipose tissue (eWAT). Fourteen-week HFD challenge repressed TCF7L2 and β-cat S675 phosphorylation in eWAT while such repression was reversed by liraglutide treatment (150 µg/kg body weight daily) during week 10 to week 14. In Glp1r-/- mice, liraglutide failed in stimulating TCF7L2 or β-cat in eWAT. We detected Glp1r expression in mouse eWAT and its level is enriched in its \"stromal vascular fraction\" (SVF). Mouse eWAT-SVF showed reduced expression of Tcf7l2 and its Tcf7l2 level could not be stimulated by liraglutide treatment; while following adipogenic differentiation, rat eWAT-SVF showed elevated Tcf7l2 expression. Direct in vitro liraglutide treatment in eWAT-SVF stimulated CREB S133, β-cat S675 phosphorylation, and cellular cAMP level. Thus, cAMP/β-cat signaling cascade can be stimulated by liraglutide in eWAT via GLP-1R expressed in eWAT-SVF.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46397261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Insights of the role of estrogen in obesity from two models of ERα deletion. 雌激素在两种ERα缺失模型中肥胖症中的作用

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-04-05 DOI: 10.1530/JME-21-0260

Rocío Del M Saavedra-Peña, Natalia Taylor, Matthew S Rodeheffer

{"title":"Insights of the role of estrogen in obesity from two models of ERα deletion.","authors":"Rocío Del M Saavedra-Peña, Natalia Taylor, Matthew S Rodeheffer","doi":"10.1530/JME-21-0260","DOIUrl":"10.1530/JME-21-0260","url":null,"abstract":"Sex hormones play a pivotal role in physiology and disease. Estrogen, the female sex hormone, has been long implicated in having protective roles against obesity. However, the direct impact of estrogens in white adipose tissue (WAT) function and growth is not understood. Here, we show that the deletion of estrogen receptor alpha (ERα; Esr1) from adipocytes using Adipoq-credoes not affect adipose mass in male or female mice under normal or high-fat diet (HFD) conditions. However, loss of ERα in adipocyte precursor cells (APs) via Pdgfra-cre leads to exacerbated obesity upon HFD feeding in both male and female mice, with s.c. adipose (SWAT)-specific expansion in male mice. Further characterization of these mice revealed infertility and increased plasma levels of sex hormones, including estradiol in female mice and androgens in male mice. These findings compromise the study of estrogen signaling within the adipocyte lineage using the Pdgfra-crestrain. However, AP transplant studies demonstrate that the increased AP hyperplasia in male SWAT upon Pdgfra-cre-mediated ablation of ERα is not driven by AP-intrinsic mechanisms but is rather mediated by off-target effects. These data highlight the inherent difficulties in studying models that disrupt the intricate balance of sex hormones. Thus, better approaches are needed to study the cellular and molecular mechanisms of sex hormones in obesity and disease.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"68 4","pages":"179-194"},"PeriodicalIF":3.5,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173145/pdf/nihms-1887822.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9818152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

The AR in bone marrow progenitor cells protects against short-term high caloric diet induced weight gain in male mice. 骨髓祖细胞中的AR对短期高热量饮食引起的雄性小鼠体重增加具有保护作用。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-04-01 DOI: 10.1530/JME-22-0038

V. Venkatesh, P. K. Russell, Barbara Fam White, Michele V. Clarke, S. Golub, Salvatore Mangiofico, Christian Haralambous, J. Lokan, S. Andrikopoulos, J. Zajac, R. Davey

{"title":"The AR in bone marrow progenitor cells protects against short-term high caloric diet induced weight gain in male mice.","authors":"V. Venkatesh, P. K. Russell, Barbara Fam White, Michele V. Clarke, S. Golub, Salvatore Mangiofico, Christian Haralambous, J. Lokan, S. Andrikopoulos, J. Zajac, R. Davey","doi":"10.1530/JME-22-0038","DOIUrl":"https://doi.org/10.1530/JME-22-0038","url":null,"abstract":"We previously identified a novel pathway of testosterone action via the androgen receptor (AR) in bone marrow mesenchymal precursor cells (BM-PCs) to negatively regulate fat mass and improve metabolic function in male mice. This was achieved using our PC-AR Gene Replacement mouse model in which the AR is only expressed in BM-PCs and deleted in all other tissues. We hypothesise that the markedly reduced fat mass and increased insulin sensitivity of PC-AR Gene Replacements will confer protection from diet-induced overweight and obesity. To test this, 6-week-old male PC-AR Gene Replacements and controls (wild-type (WT), Global-AR knockouts (KOs)) were fed a chow or high caloric diet (HCD) for 8 or 18 weeks. Following 8 weeks (short-term) of HCD, WT and Global-ARKOs had markedly increased subcutaneous white adipose tissue (WAT) and retroperitoneal visceral adipose tissue (VAT) mass compared to chow-fed controls. In contrast, PC-AR Gene Replacements were resistant to WAT and VAT accumulation following short-term HCD feeding accompanied by fewer large adipocytes and upregulation of expression of the metabolic genes Acaca and Pnlpa2. Following long-term HCD feeding for 18 weeks, the PC-AR Gene Replacements were no longer resistant to increased WAT and VAT adiposity; however, maintained their improved whole-body insulin sensitivity with an increased rate of glucose disappearance and increased glucose uptake into subcutaneous WAT. In conclusion, testosterone action via the AR in BM-PCs to negatively regulate fat mass and improve metabolism, confers resistance from short-term diet induced weight gain and partial protection from long-term diet induced obesity in male mice.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43048526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reviewing the physiological roles of the novel hormone-receptor pair INSL5-RXFP4: a protective energy sensor? 新型激素受体对INSL5-RXFP4的生理作用综述:保护性能量传感器?

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-04-01 DOI: 10.1530/JME-21-0241

D. Hechter, Brett Vahkal, Tiana Tiede, S. Good

{"title":"Reviewing the physiological roles of the novel hormone-receptor pair INSL5-RXFP4: a protective energy sensor?","authors":"D. Hechter, Brett Vahkal, Tiana Tiede, S. Good","doi":"10.1530/JME-21-0241","DOIUrl":"https://doi.org/10.1530/JME-21-0241","url":null,"abstract":"There is no common consensus for the physiological role of insulin-like peptide 5 (INSL5) and its cognate receptor, relaxin family peptide receptor 4 (RXFP4). The experimental data for INSL5-RXFP4 expression and function point to a potential role of the peptide hormone and receptor pair in linking energy availability, homeostasis and inflammation. In this review, we summarize studies on the INSL5-RXFP4 system and propose that the current findings from diverse experimental settings point broadly to a role as a protective energy sensor (PES). Specifically, we review the evidence that (1) INSL5-RXFP4 could regulate immune response by decreasing the production of proinflammatory cytokines and may be involved in the stress response via the HPA axis; (2) INSL5-RXFP4 may signal through sensory neurons on the vagus nerve, transmitting signals to the central nervous system; and (3) INSL5-RXFP4 could have local autocrine/paracrine roles within the intestinal tract and immune cells. Further investigation and clarification of these proposed roles of INSL5-RXFP4 may prove a greater physiological relevance for the pair and add to existing evidence of INSL5-RXFP4 role as a PES.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42374856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Endocrine and molecular factors of increased female reproductive performance in the Dummerstorf high-fertility mouse line FL1 Dummerstorf高生育率小鼠系FL1雌性繁殖性能提高的内分泌和分子因素

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-04-01 DOI: 10.1530/JME-22-0012

C. Ludwig, Simon Bohleber, A. Rebl, E. Wirth, M. T. Venuto, M. Langhammer, U. Schweizer, J. Weitzel, M. Michaelis

{"title":"Endocrine and molecular factors of increased female reproductive performance in the Dummerstorf high-fertility mouse line FL1","authors":"C. Ludwig, Simon Bohleber, A. Rebl, E. Wirth, M. T. Venuto, M. Langhammer, U. Schweizer, J. Weitzel, M. Michaelis","doi":"10.1530/JME-22-0012","DOIUrl":"https://doi.org/10.1530/JME-22-0012","url":null,"abstract":"The Dummerstorf high-fertility mouse line FL1 is a worldwide unique selection experiment for increased female reproductive performance. After more than 190 generations of selection, these mice doubled the amount of offspring per litter compared to the unselected control line. FL1 females have a superior lifetime fecundity and the highest Silver fecundity index that has been described in mice, while their offspring show no signs of growth retardation. The reasons for the increased reproductive performance remained unclear. Thus, this study aims to characterize the Dummerstorf high-fertility mouse line FL1 on endocrine and molecular levels on the female side. We analyzed parameters of the hypothalamic pituitary gonadal axis on both hormonal and transcriptional levels. Gonadotropin-releasing hormone and follicle-stimulating hormone (FSH) concentrations were decreased in FL1 throughout the whole estrous cycle. Luteinizing hormone (LH) was increased in FL1 mice in estrus. Progesterone concentrations were decreased in estrus in FL1 mice and not affected in diestrus. We used a holistic gene expression approach in the ovary to obtain a global picture of how the high-fertility phenotype is achieved. We found several differentially expressed genes in the ovaries of FL1 mice that are associated with different female fertility traits. Our results indicate that ovulation rates in mice can be increased despite decreased FSH levels. Cycle-related alterations of progesterone and LH levels have the potential to improve follicular maturation, and interactions of endocrine and molecular factors lead to enhanced follicular survival, more successful folliculogenesis and therefore higher ovulation rates in female FL1 mice.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"69 1","pages":"285 - 298"},"PeriodicalIF":3.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47070557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Evidence that nuclear receptors are related to terpene synthases. 核受体与萜烯合成酶有关的证据。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-03-14 DOI: 10.1530/JME-21-0156

Douglas R Houston, Jane G Hanna, J Constance Lathe, Stephen G Hillier, Richard Lathe

{"title":"Evidence that nuclear receptors are related to terpene synthases.","authors":"Douglas R Houston, Jane G Hanna, J Constance Lathe, Stephen G Hillier, Richard Lathe","doi":"10.1530/JME-21-0156","DOIUrl":"https://doi.org/10.1530/JME-21-0156","url":null,"abstract":"Ligand-activated nuclear receptors (NRs) orchestrate development, growth, and reproduction across all animal lifeforms - the Metazoa - but how NRs evolved remains mysterious. Given the NR ligands including steroids and retinoids are predominantly terpenoids, we asked whether NRs might have evolved from enzymes that catalyze terpene synthesis and metabolism. We provide evidence suggesting that NRs may be related to the terpene synthase (TS) enzyme superfamily. Based on over 10,000 3D structural comparisons, we report that the NR ligand-binding domain and TS enzymes share a conserved core of seven α-helical segments. In addition, the 3D locations of the major ligand-contacting residues are also conserved between the two protein classes. Primary sequence comparisons reveal suggestive similarities specifically between NRs and the subfamily of cis-isoprene transferases, notably with dehydrodolichyl pyrophosphate synthase and its obligate partner, NUS1/NOGOB receptor. Pharmacological overlaps between NRs and TS enzymes add weight to the contention that they share a distant evolutionary origin, and the combined data raise the possibility that a ligand-gated receptor may have arisen from an enzyme antecedent. However, our findings do not formally exclude other interpretations such as convergent evolution, and further analysis will be necessary to confirm the inferred relationship between the two protein classes.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"68 3","pages":"153-166"},"PeriodicalIF":3.5,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39581341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

C-peptide attenuates hyperglycemia-induced pulmonary fibrosis by inhibiting transglutaminase 2. C肽通过抑制转谷氨酰胺酶2来减轻高血糖诱导的肺纤维化。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-03-01 DOI: 10.1530/JME-21-0271

Hye-Yoon Jeon, Ah-Jun Lee, Eun-bin Kim, Minsoo Kim, W. Park, Kwon-Soo Ha

{"title":"C-peptide attenuates hyperglycemia-induced pulmonary fibrosis by inhibiting transglutaminase 2.","authors":"Hye-Yoon Jeon, Ah-Jun Lee, Eun-bin Kim, Minsoo Kim, W. Park, Kwon-Soo Ha","doi":"10.1530/JME-21-0271","DOIUrl":"https://doi.org/10.1530/JME-21-0271","url":null,"abstract":"Proinsulin C-peptide has a protective effect against diabetic complications; however, its role in hyperglycemia-induced pulmonary fibrosis is unknown. In this study, we investigated the inhibitory effect of C-peptide on hyperglycemia-induced pulmonary fibrosis and the molecular mechanism of C-peptide action in the lungs of diabetic mice and in human pulmonary microvascular endothelial cells (HPMVECs). We found that, in the lungs of diabetic mice, C-peptide supplementation using osmotic pumps attenuated hyperglycemia-induced pulmonary fibrosis and expression of fibrosis-related proteins. In HPMVECs, C-peptide inhibited vascular endothelial growth factor-induced adherens junction disruption and endothelial cell permeability by inhibiting reactive oxygen species generation and transglutaminase (TGase) activation. In the lungs, C-peptide supplementation suppressed hyperglycemia-induced ROS generation, TGase activation, and microvascular leakage. C-peptide inhibited hyperglycemia-induced inflammation and apoptosis, which are involved in the pathological process of pulmonary fibrosis. We also demonstrated the role of TGase2 in hyperglycemia-induced vascular leakage, inflammation, apoptosis, and pulmonary fibrosis in the lungs of diabetic TGase2-null (Tgm2-/-) mice. Furthermore, we demonstrated a long-term inhibitory effect of systemic delivery of C-peptide using K9-C-peptide hydrogels on hyperglycemia-induced fibrosis in diabetic lungs. Overall, our findings suggest that C-peptide alleviates hyperglycemia-induced pulmonary fibrosis by inhibiting TGase2-mediated microvascular leakage, inflammation, and apoptosis in diabetes.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42940174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5