Journal of molecular endocrinology最新文献_第9页

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

Telmisartan is the most effective ARB to increase adiponectin via PPARα in adipocyte. 替米沙坦是通过脂肪细胞PPARα增加脂联素最有效的ARB。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-03-01 DOI: 10.1530/JME-21-0239

N. Hattori, Ayato Yamada, Shunya Nakatsuji, Takeshi Matsuda, Norito Nishiyama, A. Shimatsu

{"title":"Telmisartan is the most effective ARB to increase adiponectin via PPARα in adipocyte.","authors":"N. Hattori, Ayato Yamada, Shunya Nakatsuji, Takeshi Matsuda, Norito Nishiyama, A. Shimatsu","doi":"10.1530/JME-21-0239","DOIUrl":"https://doi.org/10.1530/JME-21-0239","url":null,"abstract":"Telmisartan and irbesartan are angiotensin II receptor blockers (ARBs) and reportedly stimulate adiponectin secretion from adipocytes via partial peroxisome proliferator-activated receptor γ (PPARγ) activation. However, quantitative evaluation among different ARBs hasn't been performed. Adiponectin exerts strong protection against a number of pathological events by suppressing cell death, inhibiting inflammation and enhancing cell survival, while leptin promotes inflammation, oxidative stress, atherogenesis and thrombosis. The aim of this study was to identify the most effective ARB enhancing adiponectin secretion without raising leptin secretion from human white adipocytes (HWAs). Among seven ARBs (azilsartan, candesartan, irbesartan, losartan, olmesartan, telmisartan, valsartan), telmisartan was the most effective ARB for the increase of adiponectin secretion, and irbesartan was the second, whereas the other ARBs at 1 µM had no effect on adiponectin secretion. GW9662, a PPARγ antagonist, completely blocked pioglitazone (PPARγ agonist)-induced adiponectin secretion and mRNA expression, whereas it unexpectedly blocked neither telmisartan- nor irbesartan-induced adiponectin secretion and mRNA expression, but rather increased them. GW6471, PPARα antagonist, and siRNA for PPARα suppressed telmisartan- and irbesartan-induced adiponectin secretion, suggesting that PPARα is the main target of these ARBs to increase adiponectin secretion in HWAs. Leptin secretion was not affected by any ARBs at 1 µM and GW9662 significantly decreased the basal secretion of leptin, suggesting that basal leptin secretion is regulated in a PPARγ dependent manner. We conclude that telmisartan is the most effective ARB to increase adiponectin secretion via PPARα without raising leptin secretion from HWAs.","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":"43641045","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

Synoviolin inhibits the inflammatory cytokine secretion of Müller cells by reducing NLRP3. 滑膜小提琴通过降低NLRP3抑制<s:1> ller细胞的炎性细胞因子分泌。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-01-25 DOI: 10.1530/JME-21-0123

Jiayu Zhang, Chengwei Chen, Liang Wu, Qiang Wang, Jiawei Chen, Sifang Zhang, Zhenguo Chen

{"title":"Synoviolin inhibits the inflammatory cytokine secretion of Müller cells by reducing NLRP3.","authors":"Jiayu Zhang, Chengwei Chen, Liang Wu, Qiang Wang, Jiawei Chen, Sifang Zhang, Zhenguo Chen","doi":"10.1530/JME-21-0123","DOIUrl":"https://doi.org/10.1530/JME-21-0123","url":null,"abstract":"The pro-inflammatory cytokines secreted by Müller cells aggregate retinal cell loss and vascularization in diabetic retinopathy (DR). The deubiquitinase BRCA1-BRCA2-containing complex subunit 3 (BRCC3)-mediated nucleotide-binding domain and leucine-rich repeat receptor containing a pyrin domain 3 (NLRP3) inflammasome activation participate in this progress. This study aims to clarify whether the E3 ubiquitin ligase synoviolin (SYVN1) relieves DR via regulating the BRCC3/NLRP3 axis. The DR model was established using streptozotocin-induced mice. Immunofluorescence staining with anti-CD31, anti-glutamine synthetase, and anti-vimentin was performed to identify DR and Müller cells. Levels of pro-inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, IL-6, and IL-18, in murine serum and Müller cell supernatants were determined. Co-immunoprecipitation (Co-IP) and ubiquitination assays were used to clarify the interactions among SYVN1, BRCC3, and NLRP3. SYVN1 was reduced and BRCC3 was increased in DR retina and high glucose (HG)-induced Müller cells. Overexpressing 1 promoted the ubiquitination and degradation of BRCC3 and reduced the secretion of proinflammatory cytokines in HG-induced Müller cells. The simultaneous overexpression of 1 and Brcc3 restored the reduction of pro-inflammatory cytokines caused by the overexpression of 1 alone. Co-IP experiments confirmed the interaction between BRCC3 and NLRP3. SYVN1-mediated BRCC3 downregulation promoted NLRP3 ubiquitination and reduced pro-inflammatory cytokine secretion. 1 overexpression reduced retinal vascularization and inflammatory cytokine secretion in DR mice. SYVN1 has a protective effect on DR, whose molecular mechanisms are partly through SYVN1-mediated ubiquitination of BRCC3 and the subsequent downregulation of NLRP3.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"68 2","pages":"125-136"},"PeriodicalIF":3.5,"publicationDate":"2022-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39952482","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: 7

Effects of melatonin on the production of GnRH and LH in luteal cells of pregnant sows. 褪黑素对妊娠母猪黄体细胞生成GnRH和LH的影响。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-01-20 DOI: 10.1530/JME-21-0155

Wenlong Zhang, Zelin Zhang, Jiang Peng, Sitian Yang, Dewen Tong

{"title":"Effects of melatonin on the production of GnRH and LH in luteal cells of pregnant sows.","authors":"Wenlong Zhang, Zelin Zhang, Jiang Peng, Sitian Yang, Dewen Tong","doi":"10.1530/JME-21-0155","DOIUrl":"10.1530/JME-21-0155","url":null,"abstract":"Effects of melatonin on the release and synthesis of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) at the hypothalamus and pituitary levels have been explored in some species, but a similar study in the corpora lutea (CL) has not yet been conducted. In this study, the immunostaining for GnRH and LH was observed in luteal cells of porcine CL during pregnancy, and a significant effect of pregnant stage on the level of GnRH and LH was found; higher values for GnRH and LH immunostaining and mRNA were detected in the early and mid-stages CL than in the later-stage CL (P < 0.01). Furthermore, the patterns of melatonin membrane receptors (MT1 and MT2) expression were consistent with those of GnRH and LH expression in the CL of pregnant sows; the relative levels of MT1 and MT2 in the early and mid-stages were significantly higher than those in the later-stage (P < 0.01). In luteal cells, melatonin dose-dependently increased in GnRH and LH secretion and mRNA expression. Melatonin also increased the GnRH-induced accumulation of LH and the LH-induced secretion of P4 in luteal cells. Additionally, the effects of melatonin on luteal GnRH and LH production were blocked by luzindole, a non-selective MT1 and MT2 receptor antagonist. Our results demonstrate the stimulatory effects of melatonin on GnRH and LH production in luteal cells of pregnant sows, suggesting a potential role for melatonin in luteal function through regulating the release and synthesis of GnRH and LH in luteal cells.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"68 2","pages":"111-123"},"PeriodicalIF":3.5,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39604507","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

miR-514a-3p: a novel SHP-2 regulatory miRNA that modulates human cytotrophoblast proliferation. miR-514a-3p:一种新的SHP-2调节miRNA，可调节人细胞滋养细胞增殖。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-01-20 DOI: 10.1530/JME-21-0175

Rachel C Quilang, Sylvia Lui, Karen Forbes

{"title":"miR-514a-3p: a novel SHP-2 regulatory miRNA that modulates human cytotrophoblast proliferation.","authors":"Rachel C Quilang, Sylvia Lui, Karen Forbes","doi":"10.1530/JME-21-0175","DOIUrl":"10.1530/JME-21-0175","url":null,"abstract":"Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP-2), encoded by the PTPN11 gene, forms a central component of multiple signalling pathways and is required for insulin-like growth factor (IGF)-induced placental growth. Altered expression of SHP-2 is associated with aberrant placental and fetal growth indicating that drugs modulating SHP-2 expression may improve adverse pregnancy outcome associated with altered placental growth. We have previously demonstrated that placental PTPN11/SHP-2 expression is controlled by miRNAs. SHP-2 regulatory miRNAs may have therapeutic potential; however, the individual miRNA(s) that regulate SHP-2 expression in the placenta remain to be established. We performed in silico analysis of 3'UTR target prediction databases to identify libraries of Hela cells transfected with individual miRNA mimetics, enriched in potential SHP-2 regulatory miRNAs. Analysis of PTPN11 levels by quantitative (q) PCR revealed that miR-758-3p increased, while miR-514a-3p reduced PTPN11 expression. The expression of miR-514a-3p and miR-758-3p within the human placenta was confirmed by qPCR; miR-514a-3p (but not miR-758-3p) levels inversely correlated with PTPN11 expression. To assess the interaction between these miRNAs and PTPN11/SHP-2, specific mimetics were transfected into first-trimester human placental explants and then cultured for up to 4 days. Overexpression of miR-514a-3p, but not miR-758-3p, significantly reduced PTPN11 and SHP-2 expression. microRNA-ribonucleoprotein complex (miRNP)-associated mRNA assays confirmed that this interaction was direct. miR-514a-3p overexpression attenuated IGF-I-induced trophoblast proliferation (BrdU incorporation). miR-758-3p did not alter trophoblast proliferation. These data demonstrate that by modulating SHP-2 expression, miR-514a-3p is a novel regulator of IGF signalling and proliferation in the human placenta and may have therapeutic potential in pregnancies complicated by altered placental growth.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"68 2","pages":"99-110"},"PeriodicalIF":3.5,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39634998","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: 2

HDL promotes adiponectin gene expression via the CAMKK/CAMKIV pathway. HDL通过CAMKK/CAMKIV途径促进脂联素基因表达。

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2022-01-10 DOI: 10.1530/JME-20-0211

Toshihiro Kobayashi, Hitomi Imachi, Kensaku Fukunaga, Jingya Lyu, Seisuke Sato, Takanobu Saheki, Tomohiro Ibata, Mari Matsumoto, Salimah B Japar, Koji Murao

{"title":"HDL promotes adiponectin gene expression via the CAMKK/CAMKIV pathway.","authors":"Toshihiro Kobayashi, Hitomi Imachi, Kensaku Fukunaga, Jingya Lyu, Seisuke Sato, Takanobu Saheki, Tomohiro Ibata, Mari Matsumoto, Salimah B Japar, Koji Murao","doi":"10.1530/JME-20-0211","DOIUrl":"https://doi.org/10.1530/JME-20-0211","url":null,"abstract":"Adiponectin (APN) is an adipokine that protects against diabetes and atherosclerosis. High-density lipoprotein (HDL) mediates reverse cholesterol transport, which also protects against atherosclerosis. In this process, the human homolog of the B class type I scavenger receptor (SR-BI/CLA-1) facilitates the cellular uptake of cholesterol from HDL. The level of circulating APN is positively correlated with the serum level of HDL-cholesterol. In this study, we investigated whether HDL stimulates the gene expression of APN through the Ca2+/calmodulin (CaM)-dependent protein kinase IV (CaMKIV) cascade. APN expression was examined using real-time PCR and western blot analysis in 3T3-L1 cells incubated with HDL. CaMKIV activity was assessed by the detection of activation loop phosphorylation (at Thr196 residue), and the effect of the constitutively active form, CaMKIVc, on APN promoter activity was investigated. Our results showed that HDL stimulated APN gene expression via hSR-BI/CLA-1. Furthermore, we explored the signaling pathways by which HDL stimulated APN expression in 3T3-L1 cells. The stimulation of APN gene expression by HDL appears to be mediated by CaMKK, as STO-609, a specific inhibitor of CaMKK2, prevents this effect. We revealed that CaMKIVc increased APN gene transcriptional activity, and the CaMKIV-dominant negative mutant blocked the effect of HDL on APN promoter activity. Finally, knockdown of hSR-BI/CLA-1 also canceled the effect of HDL on APN gene expression. These results suggest that HDL has an important role to improve the function of adipocytes by activating hSR-BI/CLA-1, and CaMKK/CaMKIV pathway is conceivable as one of the signaling pathways of this activation mechanism.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":"68 2","pages":"89-98"},"PeriodicalIF":3.5,"publicationDate":"2022-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39767110","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: 4