Journal of molecular endocrinology最新文献_第10页

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

miR-146a promotes M2 macrophage polarization and accelerates diabetic wound healing by inhibiting the TLR4/NF-κB axis. miR-146a通过抑制TLR4/NF-κB轴促进M2巨噬细胞极化，加速糖尿病创面愈合。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-03-01 DOI: 10.1530/jme-21-0019

Xuefeng Peng, Fang He, Yanling Mao, Yihui Lin, Jingwen Fang, Yangchun Chen, Zhichun Sun, Yafen Zhuo, Jianjia Jiang

{"title":"miR-146a promotes M2 macrophage polarization and accelerates diabetic wound healing by inhibiting the TLR4/NF-κB axis.","authors":"Xuefeng Peng, Fang He, Yanling Mao, Yihui Lin, Jingwen Fang, Yangchun Chen, Zhichun Sun, Yafen Zhuo, Jianjia Jiang","doi":"10.1530/jme-21-0019","DOIUrl":"https://doi.org/10.1530/jme-21-0019","url":null,"abstract":"We tried to unveil the clinical significance of miR-146a as a biomarker in M2 macrophage polarization in diabetic wound healing. Initially, we found reduced miR-146a in macrophages of diabetic patients. Next, dual-luciferase assay verified that toll-like receptor 4 (TLR4) was a target gene of miR-146 and was negatively regulated by miR-146. Moreover, after ectopic expression and depletion experiments of miR-146 and/or TLR4, lipopolysaccharide-induced inflammatory response of macrophages was detected. The results revealed that overexpression of miR-146a promoted the M2 macrophage polarization by suppressing the TLR4/nuclear factor-kappaB (NF-κB) axis, so as to enhance wound healing in diabetic ulcers. Further, mouse models with diabetic ulcers were established to investigate the effects of miR-146a on diabetic wound healing in vivo, which revealed that miR-146a promoted wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis. In conclusion, we demonstrate that miR-146a can induce M2 macrophage polarization to enhance wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"69 2 1","pages":"315-327"},"PeriodicalIF":3.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45492098","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: 16

A PPAR-alpha agonist and DPP-4 inhibitor mitigate adipocyte dysfunction in obese mice. ppar - α激动剂和DPP-4抑制剂可减轻肥胖小鼠的脂肪细胞功能障碍。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-03-01 DOI: 10.1530/JME-21-0084

Daiana Araujo Santana-Oliveira, Aline Fernandes-da-Silva, Carolline Santos Miranda, F. F. Martins, C. Mandarim-de-Lacerda, V. Souza-Mello

{"title":"A PPAR-alpha agonist and DPP-4 inhibitor mitigate adipocyte dysfunction in obese mice.","authors":"Daiana Araujo Santana-Oliveira, Aline Fernandes-da-Silva, Carolline Santos Miranda, F. F. Martins, C. Mandarim-de-Lacerda, V. Souza-Mello","doi":"10.1530/JME-21-0084","DOIUrl":"https://doi.org/10.1530/JME-21-0084","url":null,"abstract":"Obesity causes white and brown adipocyte dysfunction, reducing browning and stimulating whitening. Drugs that tackle adipocyte dysfunction through thermogenesis stimulation could be used to treat obesity. This study sought to address whether a combination of the PPAR-alpha agonist (WY14643) and DPP4i (linagliptin) potentiates browning and mitigates adipose tissue dysfunction, emphasizing the pathways related to browning induction and the underlying thermogenesis in high-fat-fed mice. Adult male C57BL/6 mice were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for twelve weeks. Experiment 1 aimed to evaluate whether five weeks of combined therapy was able to potentiate browning using a five-group design: C, HF, HFW (monotherapy with WY14643, 2.5 mg/kg body mass), HFL (monotherapy with linagliptin, 15 mg/kg body mass), and HFC (a combination of both drugs). Experiment 2 further addressed the pathways involved in browning maximization using a four-group study design: C, CC (C diet plus the drug combination), HF, and HFC (HF diet plus the drug combination). The HF group showed overweight, oral glucose intolerance, sWAT adipocyte hypertrophy, and reduced numerical density of nuclei per area of BAT, confirming whitening. Only the combined treatment normalized these parameters in addition to body temperature increases, browning induction, and whitening rescue. The high expression of thermogenic marker genes parallel to reduced expression of inflammatory and endoplasmic reticulum stress genes mediated the beneficial findings. Hence, the PPAR-alpha agonist and DPP-4i combination is a promising target for obesity control by inducing functional brown adipocytes, browning of sWAT, and enhanced adaptive thermogenesis.","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":"48346210","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

Glucocorticoids inhibit the maturation of committed osteoblasts via SOX2. 糖皮质激素通过SOX2抑制定向成骨细胞的成熟。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-03-01 DOI: 10.1530/JME-21-0213

J. Chen, Chen Shen, Haram Oh, Ji Hyun Park

{"title":"Glucocorticoids inhibit the maturation of committed osteoblasts via SOX2.","authors":"J. Chen, Chen Shen, Haram Oh, Ji Hyun Park","doi":"10.1530/JME-21-0213","DOIUrl":"https://doi.org/10.1530/JME-21-0213","url":null,"abstract":"During bone formation, mesenchymal progenitor cells mature into bone-forming osteoblasts after undergoing several stages of differentiation. Impaired bone formation is a predominant finding in glucocorticoid (GC)-induced osteoporosis (GIO). Osteoblasts at different stages of maturation can be affected by excessive endogenous or therapeutic GCs. Sex-determining region Y-box 2 (SOX2) is normally expressed in immature osteoblasts, but its overexpression can suppress osteoblast differentiation. This study aimed to evaluate whether GC affects SOX2 expression in osteoblasts, and whether SOX2 contributes to GC-induced inhibition of osteoblast differentiation. Treatment with GCs such as dexamethasone (Dex) or hydrocortisone enhanced SOX2 expression. Silencing SOX2 improved inhibition of GC-induced osteoblast differentiation, whereas SOX2 overexpression decreased mineralized nodule formation and RUNX2 and Osterix expression in MC3T3-E1 cells. On the contrary, when C3H10T1/2 uncommitted mesenchymal stem cells were subjected to SOX2 overexpression, RUNX2 expression increased. As a mechanism of Dex-induced SOX2 upregulation in preosteoblasts, we found that the STAT3 pathway or GC receptor (GR) is involved using a GR antagonist, STAT3 regulators, and chromatin immunoprecipitation assays. Moreover, mice treated with Dex for four weeks showed a notable increase in SOX2 expression in the bones and an increased ratio of procollagen type 1 N-terminal propeptide to osteocalcin in the plasma than in control mice. This study demonstrated that GC enhances SOX2 expression in vitro in osteoblast and in vivo in the mice bone, which affects bone-forming activity differently depending on the differentiation stage of osteoblast-lineage cells. Our results provide new insights into prevention and treatment against impaired bone formation in GIO.","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":"46446480","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

Vitamin D receptor regulates proliferation and differentiation of thyroid carcinoma via the E-cadherin-β-catenin complex. 维生素D受体通过E-cadherin-β-catenin复合物调节甲状腺癌的增殖和分化。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-03-01 DOI: 10.1530/JME-21-0167

Yali Ling, Feng Xu, Xuedi Xia, Dexing Dai, Ruoman Sun, Zhongjian Xie

{"title":"Vitamin D receptor regulates proliferation and differentiation of thyroid carcinoma via the E-cadherin-β-catenin complex.","authors":"Yali Ling, Feng Xu, Xuedi Xia, Dexing Dai, Ruoman Sun, Zhongjian Xie","doi":"10.1530/JME-21-0167","DOIUrl":"https://doi.org/10.1530/JME-21-0167","url":null,"abstract":"Thyroid cancer has the fastest rising incidence among cancers, especially for differentiated thyroid carcinoma (DTC). Although the prognosis of DTC is relatively good, if it changes to anaplastic thyroid carcinoma (ATC), the prognosis will be very poor. The prognosis of DTC is largely depending on the degree of cell differentiation and proliferation. However, whether the vitamin D receptor (VDR) plays a role in regulating the proliferation and the differentiation of DTC cells is unclear. In the present study, we found that VDR was upregulated in DTC tissues compared to the adjacent non-cancerous tissue. Knockdown of VDR increased proliferation and decreased differentiation proliferation in DTC cells in vitro as well as DTC cell-derived xenografts in vivo. In contrast, overexpression of VDR had an opposite effect. Knockdown of E-cadherin abolished VDR-induced suppression of proliferation and enhancement of differentiation of the DTC cells. Knockdown of β-catenin partially reversed the effect of the VDR knockdown. VDR increases the levels of E-cadherin in the plasma membrane and decreases the levels of β-catenin in the nucleus. VDR binds to E-cadherin and β-catenin in the plasma membrane of the DTC cell. Taken together, VDR inhibits DTC cell proliferation and promotes differentiation via regulation of the E-cadherin/β-catenin complex, potentially representing novel clues for a therapeutic strategy to attenuate thyroid cancer progression.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"68 3","pages":"137-151"},"PeriodicalIF":3.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39574752","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

The mitochondrial profile in women with polycystic ovary syndrome: impact of exercise. 多囊卵巢综合征妇女的线粒体特征：运动的影响。

IF 3.6 4区医学

Journal of molecular endocrinology Pub Date : 2022-03-01 DOI: 10.1530/JME-21-0177

Melpomeni Malamouli, Itamar Levinger, Andrew J McAinch, Adam J Trewin, Raymond J Rodgers, Alba Moreno-Asso

{"title":"The mitochondrial profile in women with polycystic ovary syndrome: impact of exercise.","authors":"Melpomeni Malamouli, Itamar Levinger, Andrew J McAinch, Adam J Trewin, Raymond J Rodgers, Alba Moreno-Asso","doi":"10.1530/JME-21-0177","DOIUrl":"10.1530/JME-21-0177","url":null,"abstract":"Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting pre-menopausal women and involves metabolic dysregulation. Despite the high prevalence of insulin resistance, the existence of mitochondrial dysregulation and its role in the pathogenesis of PCOS is not clear. Exercise is recommended as the first-line therapy for women with PCOS. In particular, high-intensity interval training (HIIT) is known to improve metabolic health and enhance mitochondrial characteristics. In this narrative review, the existing knowledge of mitochondrial characteristics in skeletal muscle and adipose tissue of women with PCOS and the effect of exercise interventions in ameliorating metabolic and mitochondrial health in these women are discussed. Even though the evidence on mitochondrial dysfunction in PCOS is limited, some studies point to aberrant mitochondrial functions mostly in skeletal muscle, while there is very little research in adipose tissue. Although most exercise intervention studies in PCOS report improvements in metabolic health, they show diverse and inconclusive findings in relation to mitochondrial characteristics. A limitation of the current study is the lack of comprehensive mitochondrial analyses and the diversity in exercise modalities, with only one study investigating the impact of HIIT alone. Therefore, further comprehensive large-scale exercise intervention studies are required to understand the association between metabolic dysfunction and aberrant mitochondrial profile, and the molecular mechanisms underlying the exercise-induced metabolic adaptations in women with PCOS.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"68 3","pages":"R11-R23"},"PeriodicalIF":3.6,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39844937","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