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  1. AU=Guzeloglu-Kayisli Ozlem
  2. AU="Tuck, Christopher"
  3. AU=Janssens Nico AU=Janssens Nico
  4. AU="Roberto Giacomelli"
  5. AU="Zarenezhad, Elham"
  6. AU="Oyefule, Omobolanle"
  7. AU="Baskey, Swarnamayee"
  8. AU="J. Kotzka"
  9. AU=Richardson Paul D
  10. AU="Forbes, Stuart"
  11. AU="Padilla, Michele"
  12. AU="Wenaweser, Peter"
  13. AU=Jahnlova Denisa
  14. AU="Nicole Fasel"
  15. AU="Carâp, Alexandru Constantin"
  16. AU="Gruber-Wackernagel, Alexandra"
  17. AU="Ye, Sining"
  18. AU="Bekele, B Nebiyou"
  19. AU="Bolognesi, Martino"
  20. AU="Delabesse, Eric"

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  1. Artikel ; Online: Enhanced ZBTB16 Levels by Progestin-Only Contraceptives Induces Decidualization and Inflammation.

    Arlier, Sefa / Kayisli, Umit A / Semerci, Nihan / Ozmen, Asli / Larsen, Kellie / Schatz, Frederick / Lockwood, Charles J / Guzeloglu-Kayisli, Ozlem

    International journal of molecular sciences

    2023  Band 24, Heft 13

    Abstract: Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled fragile microvessels. The combination of fragile microvessels and enhanced tissue ... ...

    Abstract Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled fragile microvessels. The combination of fragile microvessels and enhanced tissue factor levels in decidualized HESCs generates excess thrombin, which contributes to abnormal uterine bleeding (AUB) by inducing inflammation, aberrant angiogenesis, and proteolysis. The- zinc finger and BTB domain containing 16 (ZBTB16) has been reported as an essential regulator of decidualization. Microarray studies have demonstrated that
    Mesh-Begriff(e) Female ; Humans ; Animals ; Guinea Pigs ; Progestins/pharmacology ; Interleukin-8/metabolism ; Thrombin/metabolism ; Contraceptive Agents ; Thromboplastin/metabolism ; Glucocorticoids/metabolism ; Cyclooxygenase 2/metabolism ; Endometrium ; Estradiol/pharmacology ; Inflammation/chemically induced ; Inflammation/metabolism ; Stromal Cells/metabolism ; Cells, Cultured ; Decidua/metabolism ; Medroxyprogesterone Acetate/adverse effects
    Chemische Substanzen Progestins ; Interleukin-8 ; Thrombin (EC 3.4.21.5) ; Contraceptive Agents ; Thromboplastin (9035-58-9) ; Glucocorticoids ; Cyclooxygenase 2 (EC 1.14.99.1) ; Estradiol (4TI98Z838E) ; Medroxyprogesterone Acetate (C2QI4IOI2G) ; ZBTB16 protein, human (147855-37-6)
    Sprache Englisch
    Erscheinungsdatum 2023-06-23
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241310532
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  2. Artikel ; Online: Regulation of Proinflammatory Molecules and Tissue Factor by SARS-CoV-2 Spike Protein in Human Placental Cells: Implications for SARS-CoV-2 Pathogenesis in Pregnant Women.

    Guo, Xiaofang / Semerci, Nihan / De Assis, Viviana / Kayisli, Umit A / Schatz, Frederick / Steffensen, Thora S / Guzeloglu-Kayisli, Ozlem / Lockwood, Charles J

    Frontiers in immunology

    2022  Band 13, Seite(n) 876555

    Abstract: SARS-CoV-2 infects ... ...

    Abstract SARS-CoV-2 infects cells
    Mesh-Begriff(e) Angiotensin-Converting Enzyme 2 ; COVID-19 ; Cell Line, Tumor ; Cytokines/metabolism ; Endothelial Cells/pathology ; Female ; Humans ; Placenta/metabolism ; Placenta Diseases/pathology ; Pregnancy ; Pregnancy Complications, Infectious ; Pregnant Women ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism ; Thromboplastin/metabolism
    Chemische Substanzen Cytokines ; F3 protein, human ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Thromboplastin (9035-58-9) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Sprache Englisch
    Erscheinungsdatum 2022-04-07
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.876555
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Enhanced ZBTB16 Levels by Progestin-Only Contraceptives Induces Decidualization and Inflammation

    Sefa Arlier / Umit A. Kayisli / Nihan Semerci / Asli Ozmen / Kellie Larsen / Frederick Schatz / Charles J. Lockwood / Ozlem Guzeloglu-Kayisli

    International Journal of Molecular Sciences, Vol 24, Iss 10532, p

    2023  Band 10532

    Abstract: Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled fragile microvessels. The combination of fragile microvessels and enhanced tissue ... ...

    Abstract Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled fragile microvessels. The combination of fragile microvessels and enhanced tissue factor levels in decidualized HESCs generates excess thrombin, which contributes to abnormal uterine bleeding (AUB) by inducing inflammation, aberrant angiogenesis, and proteolysis. The- zinc finger and BTB domain containing 16 (ZBTB16) has been reported as an essential regulator of decidualization. Microarray studies have demonstrated that ZBTB16 levels are induced by medroxyprogesterone acetate (MPA) and etonogestrel (ETO) in cultured HESCs. We hypothesized that pLARC-induced ZBTB16 expression contributes to HESC decidualization, whereas prolonged enhancement of ZBTB16 levels triggers an inflammatory milieu by inducing pro-inflammatory gene expression and tissue-factor-mediated thrombin generation in decidualized HESCs. Thus, ZBTB16 immunostaining was performed in paired endometria from pre- and post-depo-MPA (DMPA)-administrated women and oophorectomized guinea pigs exposed to the vehicle, estradiol (E 2 ), MPA, or E 2 + MPA. The effect of progestins including MPA, ETO, and levonorgestrel (LNG) and estradiol + MPA + cyclic-AMP (E 2 + MPA + cAMP) on ZBTB16 levels were measured in HESC cultures by qPCR and immunoblotting. The regulation of ZBTB16 levels by MPA was evaluated in glucocorticoid-receptor-silenced HESC cultures. ZBTB16 was overexpressed in cultured HESCs for 72 h followed by a ± 1 IU/mL thrombin treatment for 6 h. DMPA administration in women and MPA treatment in guinea pigs enhanced ZBTB16 immunostaining in endometrial stromal and glandular epithelial cells. The in vitro findings indicated that: (1) ZBTB16 levels were significantly elevated by all progestin treatments; (2) MPA exerted the greatest effect on ZBTB16 levels; (3) MPA-induced ZBTB16 expression was inhibited in glucocorticoid-receptor-silenced HESCs. Moreover, ZBTB16 overexpression in HESCs ...
    Schlagwörter decidualization ; endometrial stromal cells ; progestin-only contraceptives ; ZBTB16 ; IL-8 ; tissue factor ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 500
    Sprache Englisch
    Erscheinungsdatum 2023-06-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
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  4. Artikel ; Online: Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis.

    Ozmen, Asli / Nwabuobi, Chinedu / Tang, Zhonghua / Guo, Xiaofang / Larsen, Kellie / Guller, Seth / Blas, Jacqueline / Moore, Monica / Kayisli, Umit A / Lockwood, Charles J / Guzeloglu-Kayisli, Ozlem

    International journal of molecular sciences

    2023  Band 25, Heft 1

    Abstract: Leptin plays a crucial role in regulating energy homoeostasis, neuroendocrine function, metabolism, and immune and inflammatory responses. The adipose tissue is a main source of leptin, but during pregnancy, leptin is also secreted primarily by the ... ...

    Abstract Leptin plays a crucial role in regulating energy homoeostasis, neuroendocrine function, metabolism, and immune and inflammatory responses. The adipose tissue is a main source of leptin, but during pregnancy, leptin is also secreted primarily by the placenta. Circulating leptin levels peak during the second trimester of human pregnancy and fall after labor. Several studies indicated a strong association between elevated placental leptin levels and preeclampsia (PE) pathogenesis and elevated serum interleukin-6 (IL-6) levels in PE patients. Therefore, we hypothesized that a local increase in placental leptin production induces IL-6 production in Hofbauer cells (HBCs) to contribute to PE-associated inflammation. We first investigated HBCs-specific IL-6 and leptin receptor (LEPR) expression and compared their immunoreactivity in PE vs. gestational age-matched control placentas. Subsequently, we examined the in vitro regulation of IL-6 as well as the phosphorylation levels of intracellular signaling proteins STAT3, STAT5, NF-κB, and ERK1/2 by increasing recombinant human leptin concentrations (10 to 1000 ng/mL) in primary cultured HBCs. Lastly, HBC cultures were incubated with leptin ± specific inhibitors of STAT3 or STAT5, or p65 NF-κB or ERK1/2 MAPK signaling cascades to determine relevant cascade(s) involved in leptin-mediated IL-6 regulation. Immunohistochemistry revealed ~three- and ~five-fold increases in IL-6 and LEPR expression, respectively, in HBCs from PE placentas. In vitro analysis indicated that leptin treatment in HBCs stimulate IL-6 in a concentration-dependent manner both at the transcriptional and secretory levels (
    Mesh-Begriff(e) Pregnancy ; Humans ; Female ; Leptin/pharmacology ; Interleukin-6 ; STAT5 Transcription Factor ; NF-kappa B ; Pre-Eclampsia ; Placenta
    Chemische Substanzen Leptin ; Interleukin-6 ; STAT5 Transcription Factor ; NF-kappa B
    Sprache Englisch
    Erscheinungsdatum 2023-12-21
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25010135
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  5. Artikel ; Online: Dysregulated expression of GATA2 and GATA6 transcription factors in adenomyosis: implications for impaired endometrial receptivity.

    Pavlovic, Zoran Jason / Hsin-Yu Pai, Angel / Hsiao, Tzu-Ti / Yen, Chih-Feng / Alhasan, Hasan / Ozmen, Asli / New, Erika P / Guo, Xiaofang / Imudia, Anthony N / Guzeloglu-Kayisli, Ozlem / Lockwood, Charles J / Kayisli, Umit A

    F&S science

    2023  Band 5, Heft 1, Seite(n) 92–103

    Abstract: Objective: To study the effect of adenomyosis on the localized expression of the GATA binding proteins 2 and 6 (GATA2 and GATA6) zinc-finger transcription factors that are involved in proliferation of hematopoietic and endocrine cell lineages, cell ... ...

    Abstract Objective: To study the effect of adenomyosis on the localized expression of the GATA binding proteins 2 and 6 (GATA2 and GATA6) zinc-finger transcription factors that are involved in proliferation of hematopoietic and endocrine cell lineages, cell differentiation, and organogenesis, potentially leading to impaired endometrial implantation.
    Design: Laboratory based experimental study.
    Setting: Academic hospital and laboratory.
    Patients: Human endometrial stromal cells (HESCs) of reproductive age patients, 18-45 years of age, with adenomyosis were compared with patients with no pathology and leiomyomatous uteri as controls (n = 4 in each group, respectively). Additionally, midsecretory phase endometrial sections were obtained from patients with adenomyosis and control patients with leiomyoma (n = 8 in each group, respectively).
    Interventions: GATA2 and GATA6 immunohistochemistry and H-SCORE were performed on the midsecretory phase endometrial sections from adenomyosis and leiomyoma control patients (n = 8 each, respectively). Control and adenomyosis patient HESC cultures were treated with placebo or 10
    Main outcome measures: Immunohistochemistry was performed to obtain GATA2 and GATA6 H-SCORES in adenomyosis vs. control patient endometrial tissue. Expression of GATA2, GATA6, insulin-like growth factor-binding protein 1 (IGFBP1), prolactin (PRL), progesterone receptor (PGR), estrogen receptor 1 (ESR1), leukemia inhibitory factor (LIF), and Interleukin receptor 11 (IL11R) messenger RNA (mRNA) levels were analyzed using by qPCR with normalization to ACTB. Silencing and overexpression experiments also had the corresponding mRNA levels of the above factors analyzed. Western blot analysis was performed on isolated proteins from transfection experiments.
    Results: Immunohistochemistry revealed an overall fourfold lower GATA2 and fourfold higher GATA6 H-SCORE level in the endometrial stromal cells of patients with adenomyosis vs. controls. Decidual induction with EMC resulted in significantly lower GATA2, PGR, PRL and IGFBP1 mRNA levels in HESC cultures from patients with adenomyosis patient vs. controls. Leukemia inhibitory factor and IL11R mRNA levels were also significantly dysregulated in adenomyosis HESCs compared with controls. . Silencing of GATA2 expression in control HESCs induced an adenomyosis-like state with significant reductions in GATA2, increases in GATA6 and accompanying aberrations in PGR, PRL, ESR1 and LIF levels. Conversely, GATA2 overexpression via vector in adenomyosis HESCs caused partial restoration of the defective decidual response with significant increases in GATA2, PGR, PRL and LIF expression.
    Conclusion: In-vivo and in-vitro experiment results demonstrate that there is an overall inverse relationship between endometrial GATA2 and GATA6 levels in patients with adenomyosis who have diminished GATA2 levels and concurrently elevated GATA6 levels. Additionally, lower GATA2 and higher GATA6 levels, together with aberrant levels of important receptors and implantation factors, such as ESR1, PGR, IGFBP1, PRL, LIF, and IL11R mRNA in HESCs from patients with adenomyosis or GATA2-silenced control HESCs, support impaired decidualization. These effects were partially restored with GATA2 overexpression in adenomyosis HESCs, demonstrating a potential therapeutic target.
    Mesh-Begriff(e) Adolescent ; Adult ; Female ; Humans ; Middle Aged ; Young Adult ; Adenomyosis/genetics ; Adenomyosis/metabolism ; Adenomyosis/pathology ; Decidua/metabolism ; GATA2 Transcription Factor/genetics ; GATA2 Transcription Factor/metabolism ; GATA2 Transcription Factor/pharmacology ; GATA6 Transcription Factor/genetics ; GATA6 Transcription Factor/metabolism ; GATA6 Transcription Factor/pharmacology ; Leiomyoma ; Leukemia Inhibitory Factor/metabolism ; Leukemia Inhibitory Factor/pharmacology ; Prolactin/metabolism ; Prolactin/pharmacology ; RNA, Messenger/metabolism ; RNA, Small Interfering/metabolism ; RNA, Small Interfering/pharmacology ; Transcription Factors
    Chemische Substanzen GATA2 protein, human ; GATA2 Transcription Factor ; GATA6 protein, human ; GATA6 Transcription Factor ; Leukemia Inhibitory Factor ; Prolactin (9002-62-4) ; RNA, Messenger ; RNA, Small Interfering ; Transcription Factors
    Sprache Englisch
    Erscheinungsdatum 2023-11-14
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2666-335X
    ISSN (online) 2666-335X
    DOI 10.1016/j.xfss.2023.11.003
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  6. Artikel ; Online: SINE RNA of the imprinted miRNA clusters mediates constitutive type III interferon expression and antiviral protection in hemochorial placentas.

    Wickramage, Ishani / VanWye, Jeffrey / Max, Klaas / Lockhart, John H / Hortu, Ismet / Mong, Ezinne F / Canfield, John / Lamabadu Warnakulasuriya Patabendige, Hiran M / Guzeloglu-Kayisli, Ozlem / Inoue, Kimiko / Ogura, Atsuo / Lockwood, Charles J / Akat, Kemal M / Tuschl, Thomas / Kayisli, Umit A / Totary-Jain, Hana

    Cell host & microbe

    2023  Band 31, Heft 7, Seite(n) 1185–1199.e10

    Abstract: Hemochorial placentas have evolved defense mechanisms to prevent the vertical transmission of viruses to the immunologically underdeveloped fetus. Unlike somatic cells that require pathogen-associated molecular patterns to stimulate interferon production, ...

    Abstract Hemochorial placentas have evolved defense mechanisms to prevent the vertical transmission of viruses to the immunologically underdeveloped fetus. Unlike somatic cells that require pathogen-associated molecular patterns to stimulate interferon production, placental trophoblasts constitutively produce type III interferons (IFNL) through an unknown mechanism. We demonstrate that transcripts of short interspersed nuclear elements (SINEs) embedded in miRNA clusters within the placenta trigger a viral mimicry response that induces IFNL and confers antiviral protection. Alu SINEs within primate-specific chromosome 19 (C19MC) and B1 SINEs within rodent-specific microRNA cluster on chromosome 2 (C2MC) produce dsRNAs that activate RIG-I-like receptors (RLRs) and downstream IFNL production. Homozygous C2MC knockout mouse trophoblast stem (mTS) cells and placentas lose intrinsic IFN expression and antiviral protection, whereas B1 RNA overexpression restores C2MCΔ/Δ mTS cell viral resistance. Our results uncover a convergently evolved mechanism whereby SINE RNAs drive antiviral resistance in hemochorial placentas, placing SINEs as integral players in innate immunity.
    Mesh-Begriff(e) Animals ; Mice ; Female ; Pregnancy ; MicroRNAs/genetics ; Placenta ; Interferon Lambda ; Antiviral Agents ; Short Interspersed Nucleotide Elements
    Chemische Substanzen MicroRNAs ; Interferon Lambda ; Antiviral Agents
    Sprache Englisch
    Erscheinungsdatum 2023-06-13
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2023.05.018
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  7. Artikel ; Online: Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis

    Asli Ozmen / Chinedu Nwabuobi / Zhonghua Tang / Xiaofang Guo / Kellie Larsen / Seth Guller / Jacqueline Blas / Monica Moore / Umit A. Kayisli / Charles J. Lockwood / Ozlem Guzeloglu-Kayisli

    International Journal of Molecular Sciences, Vol 25, Iss 1, p

    2023  Band 135

    Abstract: Leptin plays a crucial role in regulating energy homoeostasis, neuroendocrine function, metabolism, and immune and inflammatory responses. The adipose tissue is a main source of leptin, but during pregnancy, leptin is also secreted primarily by the ... ...

    Abstract Leptin plays a crucial role in regulating energy homoeostasis, neuroendocrine function, metabolism, and immune and inflammatory responses. The adipose tissue is a main source of leptin, but during pregnancy, leptin is also secreted primarily by the placenta. Circulating leptin levels peak during the second trimester of human pregnancy and fall after labor. Several studies indicated a strong association between elevated placental leptin levels and preeclampsia (PE) pathogenesis and elevated serum interleukin-6 (IL-6) levels in PE patients. Therefore, we hypothesized that a local increase in placental leptin production induces IL-6 production in Hofbauer cells (HBCs) to contribute to PE-associated inflammation. We first investigated HBCs-specific IL-6 and leptin receptor (LEPR) expression and compared their immunoreactivity in PE vs. gestational age-matched control placentas. Subsequently, we examined the in vitro regulation of IL-6 as well as the phosphorylation levels of intracellular signaling proteins STAT3, STAT5, NF-κB, and ERK1/2 by increasing recombinant human leptin concentrations (10 to 1000 ng/mL) in primary cultured HBCs. Lastly, HBC cultures were incubated with leptin ± specific inhibitors of STAT3 or STAT5, or p65 NF-κB or ERK1/2 MAPK signaling cascades to determine relevant cascade(s) involved in leptin-mediated IL-6 regulation. Immunohistochemistry revealed ~three- and ~five-fold increases in IL-6 and LEPR expression, respectively, in HBCs from PE placentas. In vitro analysis indicated that leptin treatment in HBCs stimulate IL-6 in a concentration-dependent manner both at the transcriptional and secretory levels ( p < 0.05). Moreover, leptin-treated HBC cultures displayed significantly increased phosphorylation levels of STAT5, p65 NF-κB, and ERK1/2 MAPK and pre-incubation of HBCs with a specific ERK1/2 MAPK inhibitor blocked leptin-induced IL-6 expression. Our in situ results show that HBCs contribute to the pathogenesis of PE by elevating IL-6 expression, and in vitro results indicate that ...
    Schlagwörter preeclampsia ; placenta ; Hofbauer cells ; leptin ; IL-6 ; ERK1/2 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 630
    Sprache Englisch
    Erscheinungsdatum 2023-12-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: FKBP51 Contributes to Uterine Leiomyoma Pathogenesis by Inducing Cell Proliferation and Extracellular Matrix Deposition.

    New, Erika P / Semerci, Nihan / Ozmen, Asli / Guo, Xiaofang / Jonnalagadda, Venkata A / Kim, Joung Woul / Anderson, Matthew L / Guzeloglu-Kayisli, Ozlem / Imudia, Anthony N / Lockwood, Charles J / Kayisli, Umit A

    Reproductive sciences (Thousand Oaks, Calif.)

    2022  Band 29, Heft 6, Seite(n) 1939–1949

    Abstract: The FK506-binding protein 51 (FKBP51) binds progesterone receptor (PR), glucocorticoid receptor (GR), and androgen receptor (AR) to coregulate their transcriptional activity. We evaluated FKBP51 expression and function in human leiomyoma vs. myometrial ... ...

    Abstract The FK506-binding protein 51 (FKBP51) binds progesterone receptor (PR), glucocorticoid receptor (GR), and androgen receptor (AR) to coregulate their transcriptional activity. We evaluated FKBP51 expression and function in human leiomyoma vs. myometrial tissues and primary cultures to discover FKBP51 role(s) in the pathogenesis of leiomyomas. Quantification of in situ FKBP51 mRNA and protein levels inpaired myometrial vs. leiomyoma tissues from proliferative and secretory phases were analyzed by qPCR (n = 14), immunoblotting (n = 20), and immunohistochemistry (n = 12). Control (scramble) vs. FKBP5 siRNA-transfected leiomyoma cell cultures were assessed for proliferation, apoptosis, and mRNA levels of genes involved in cell survival and extracellular matrix (ECM) formation. Significantly higher FKBP5 mRNA levels were detected in leiomyoma vs. paired myometrium (P < 0.001). Immunoblot (P = 0.001) and immunostaining (P ≤ 0.001) confirmed increased FKBP51 levels in leiomyoma vs. paired myometrium. Compared to control siRNA transfection, FKBP5-silenced leiomyoma cell cultures displayed significantly decreased cell survival factors and reduced proliferation (P < 0.05). Moreover, qPCR analysis revealed significantly lower mRNA levels of ECM, TIPM1, and TIPM3 proteins in FKBP5-silenced leiomyoma cell cultures (P < 0.05). Increased FKBP51 expression in leiomyoma likely involves dysregulation of steroid signaling by blocking GR and PR action and promoting proliferation and ECM production. Evaluating the effect of FKBP51 inhibition in preclinical studies will clarify its significance as a potential therapeutic approach against leiomyoma.
    Mesh-Begriff(e) Cell Proliferation ; Extracellular Matrix/genetics ; Extracellular Matrix/metabolism ; Extracellular Matrix/pathology ; Female ; Humans ; Immunohistochemistry ; Leiomyoma/genetics ; Leiomyoma/metabolism ; Leiomyoma/pathology ; Myometrium/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Tacrolimus Binding Proteins/genetics ; Tacrolimus Binding Proteins/metabolism ; Uterine Neoplasms/genetics ; Uterine Neoplasms/metabolism ; Uterine Neoplasms/pathology
    Chemische Substanzen RNA, Messenger ; Tacrolimus Binding Proteins (EC 5.2.1.-) ; tacrolimus binding protein 5 (EC 5.2.1.8)
    Sprache Englisch
    Erscheinungsdatum 2022-04-14
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2276411-2
    ISSN 1933-7205 ; 1933-7191
    ISSN (online) 1933-7205
    ISSN 1933-7191
    DOI 10.1007/s43032-022-00921-2
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel: Preeclampsia is Associated With Reduced

    Ozmen, Asli / Guzeloglu-Kayisli, Ozlem / Tabak, Selcuk / Guo, Xiaofang / Semerci, Nihan / Nwabuobi, Chinedu / Larsen, Kellie / Wells, Ali / Uyar, Asli / Arlier, Sefa / Wickramage, Ishani / Alhasan, Hasan / Totary-Jain, Hana / Schatz, Frederick / Odibo, Anthony O / Lockwood, Charles J / Kayisli, Umit A

    Frontiers in cell and developmental biology

    2022  Band 10, Seite(n) 898088

    Abstract: Among several interleukin (IL)-6 family members, only IL-6 and IL-11 require a gp130 protein homodimer for intracellular signaling due to lack of intracellular signaling domain in the IL-6 receptor (IL-6R) and IL-11R. We previously reported enhanced ... ...

    Abstract Among several interleukin (IL)-6 family members, only IL-6 and IL-11 require a gp130 protein homodimer for intracellular signaling due to lack of intracellular signaling domain in the IL-6 receptor (IL-6R) and IL-11R. We previously reported enhanced decidual IL-6 and IL-11 levels at the maternal-fetal interface with significantly higher peri-membranous IL-6 immunostaining in adjacent interstitial trophoblasts in preeclampsia (PE) vs. gestational age (GA)-matched controls. This led us to hypothesize that competitive binding of these cytokines to the gp130 impairs extravillous trophoblast (EVT) differentiation, proliferation and/or invasion. Using global microarray analysis, the current study identified inhibition of interferon-stimulated gene 15 (
    Sprache Englisch
    Erscheinungsdatum 2022-06-28
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.898088
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Decidual cell FKBP51-progesterone receptor binding mediates maternal stress-induced preterm birth.

    Guzeloglu-Kayisli, Ozlem / Semerci, Nihan / Guo, Xiaofang / Larsen, Kellie / Ozmen, Asli / Arlier, Sefa / Mutluay, Duygu / Nwabuobi, Chinedu / Sipe, Bradley / Buhimschi, Irina / Buhimschi, Catalin / Schatz, Frederick / Kayisli, Umit A / Lockwood, Charles J

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Band 118, Heft 11

    Abstract: Depression and posttraumatic stress disorder increase the risk of idiopathic preterm birth (iPTB); however, the exact molecular mechanism is unknown. Depression and stress-related disorders are linked to increased FK506-binding protein 51 (FKBP51) ... ...

    Abstract Depression and posttraumatic stress disorder increase the risk of idiopathic preterm birth (iPTB); however, the exact molecular mechanism is unknown. Depression and stress-related disorders are linked to increased FK506-binding protein 51 (FKBP51) expression levels in the brain and/or
    Mesh-Begriff(e) Animals ; Female ; Mice ; Models, Animal ; Pregnancy ; Premature Birth ; Protein Binding ; RNA, Messenger/genetics ; Receptors, Progesterone/metabolism ; Stress, Physiological ; Tacrolimus Binding Proteins/genetics ; Tacrolimus Binding Proteins/metabolism
    Chemische Substanzen RNA, Messenger ; Receptors, Progesterone ; Tacrolimus Binding Proteins (EC 5.2.1.-) ; tacrolimus binding protein 5 (EC 5.2.1.8)
    Sprache Englisch
    Erscheinungsdatum 2021-04-09
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2010282118
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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