A5017351204- Estrogen and related hormone effects
- Peroxisome Proliferator-Activated Receptors
- TGF-β signaling in diseases
- Retinoids in leukemia and cellular processes
- Bone Metabolism and Diseases
- Epigenetics and DNA Methylation
- Neurobiology and Insect Physiology Research
- Vitamin D Research Studies
- Invertebrate Immune Response Mechanisms
- Growth Hormone and Insulin-like Growth Factors
- Ubiquitin and proteasome pathways
- Adipose Tissue and Metabolism
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Parathyroid Disorders and Treatments
- RNA Research and Splicing
- Metabolism, Diabetes, and Cancer
- Bone health and treatments
- Receptor Mechanisms and Signaling
- Drug Transport and Resistance Mechanisms
- Genetic Syndromes and Imprinting
- Protein Degradation and Inhibitors
- Nuclear Receptors and Signaling
- Muscle Physiology and Disorders
University of Virginia
2019-2024
University of California, San Francisco
2005-2018
The University of Tokyo
1997-2013
Japan Science and Technology Agency
1999-2001
University of Tokyo Hospital
2000
Tokyo University of Agriculture
1995
Cell proliferation and differentiation are regulated by growth regulatory factors such as transforming factor–β (TGF-β) the liphophilic hormone vitamin D. TGF-β causes activation of SMAD proteins acting coactivators or transcription in nucleus. Vitamin D controls target genes through receptor (VDR). Smad3, one downstream signaling pathway, was found mammalian cells to act a coactivator specific for ligand-induced transactivation VDR forming complex with member steroid coactivator–1 protein...
Interaction of type I collagen (COL(I)) with α2β1 integrin causes differentiation and transforming growth factor (TGF)-β receptor down-regulation in osteoblastic cells (Takeuchi, Y., Nakayama, K., Matsumoto, T. (1996) J. Biol. Chem.271, 3938–3644). The TGF-β enables to escape from the inhibition by TGF-β. To clarify how cell-matrix interaction regulates these phenotypic changes, signaling pathways were examined murine MC3T3-E1 cells. Attachment COL(I) stimulated tyrosine phosphorylation...
The nuclear vitamin D receptor (VDR) is a member of superfamily and acts as ligand-dependent transcription factor. A family cotranscriptional activators (SRC-1, TIF2, AIB-1) interacts with activates the transactivation function receptors in way. We examined interaction VDR these coactivators that was induced by several analogs, since they exert differential subsets biological action through unknown mechanisms. Unlike other analogs tested, OCT (22-oxa-1α,25-dihydroxyvitamin D3) TIF2 but not...
Atrazine (ATR) remains a widely used broadleaf herbicide in the United States despite fact that this s-chlorotriazine has been linked to reproductive abnormalities fish and amphibians. Here, using zebrafish we report environmentally relevant ATR concentrations elevated zcyp19a1 expression encoding aromatase (2.2 µg/L), increased ratio of female male (22 µg/L). selectively zcyp19a1, known gene target nuclear receptor SF-1 (NR5A1), whereas zcyp19a2, which is estrogen responsive, remained...
Abstract Estrogens and selective estrogen receptor (ER) modulators such as tamoxifen are known to increase uterine cell proliferation. Mounting evidence suggests that signaling is mediated not only by ERα ERβ nuclear receptors, but also GPR30 (GPER), a seven transmembrane (7TM) receptor. Here, we report primary human endometriotic H-38 cells express high levels of with no detectable or ERβ. Using novel analogue, STX, which activates ERs, significant stimulation the phosphatidylinositol...
We describe here a novel class of cis-acting response elements for retinoid, vitamin D, and estrogen receptors which are widely spaced (10 to 200 bp) direct repeats (DRs) the canonical 5'-AGGTCA half-site recognition motif (DR10 DR200). In contrast specificity previously observed with shortly DRs (DR1 DR5), different bind promiscuously these activate transcription in presence retinoic acid (RA), or estrogen. The greatest RA-dependent transactivation, seen DR15, was similar that DR5. Both RA...
Osteoblastic differentiation is an essential part of bone formation that compensates resorbed matrix to maintain its structural integrity. Cells in osteoblast lineage develop differentiated phenotypes during a long-term culture vitro. However, intrinsic mechanisms whereby these cells differentiate into mature osteoblasts are yet unclear. Bone morphogenetic proteins (BMPs) stimulate osteoblastic and formation. We demonstrate mouse MC3T3-E1 constitutively expressed messenger RNAs (mRNAs) for...
Structural analysis of nuclear receptor subfamily V orphan receptors suggests that ligand-independent mechanisms must regulate this subclass receptors. Here, we report steroidogenic factor 1 (SF-1) and liver homolog are repressed via posttranslational SUMO modification at conserved lysines within the hinge domain. Indeed, mutating these or adding isopeptidase SENP1 dramatically increased both native Gal4-chimera activities. The mechanism by which conjugation attenuates SF-1 activity was...
Phosphatidylinositol 4,5-bisphosphate (PIP₂) is best known as a plasma membrane-bound regulatory lipid. Although PIP₂ and phosphoinositide-modifying enzymes coexist in the nucleus, their nuclear roles remain unclear. We showed that inositol polyphosphate multikinase (IPMK), which functions both an kinase phosphoinositide 3-kinase (PI3K), interacts with receptor steroidogenic factor 1 (SF-1) phosphorylates its bound ligand, PIP₂. In vitro studies was not phosphorylated by IPMK if displaced or...
Epithelial dysfunction and crypt destruction are defining features of inflammatory bowel disease (IBD). However, current IBD therapies targeting epithelial lacking. The nuclear receptor LRH-1 (NR5A2) is expressed in intestinal epithelium thought to contribute renewal. Here we show that maintains health protects against damage. Knocking out murine organoids reduces Notch signaling, increases cell death, distorts the cellular composition epithelium, weakens barrier. Human (hLRH-1) rescues...
Abstract Cell-matrix interactions via integrins are essential for osteoblastic differentiation. We have shown that signals activated by aggregation of α2β1-integrin with type I collagen involved in the differentiation MC3T3-E1 cells. Focal adhesion kinase (FAK) is an immediate downstream signal β1-integrin, and inactivation FAK has been to disrupt To elucidate roles cells, we examined cells stably expressing antisense (asFAK) messenger RNA (mRNA). Alkaline phosphatase (ALP) activity, marker,...
CD38 is a nonlineage-restricted type II transmembrane glycoprotein possessing ecto-NAD<sup>+</sup>glycohydrolase activity. Because of its unique expression pattern in lymphocyte differentiation, it appears to function as an immunoregulatory molecule. We previously reported that was specifically induced by all-<i>trans</i>-retinoic acid (RA) human promyelocytic leukemia HL-60 cells. Here we studied the molecular mechanism RA-dependent induction CD38. The mRNA RA appeared be caused...
Excess lipid accumulation is an early signature of nonalcoholic fatty liver disease (NAFLD). Although receptor homolog 1 (LRH-1) (encoded by NR5A2) suppressed in human NAFLD, evidence linking this phospholipid-bound nuclear to hepatic metabolism lacking. Here, we report essential role for LRH-1 storage and phospholipid composition based on acute KO adult mice (LRH-1AAV8-Cre mice). Indeed, LRH-1–deficient hepatocytes exhibited large cytosolic droplets increased triglycerides (TGs). fed...
Chronic enteropathogen infection in early childhood reduces circulating insulin-like growth factor 1 (IGF1) levels and restricts growth. Pathogen-derived molecules activate host Toll-like receptors to initiate the immune response, but whether this pathway contributes inhibition is unclear. In Drosophila, activation of Toll larval fat body suppresses whole-animal Here, using a transcriptomic approach, we identify Drosophila peptide 6 (Dilp6), fat-body-derived IGF1 ortholog, as selective...
Abstract Signals from bone morphogenetic protein receptors (BMPRs) and cell adhesion to type I collagen are both important for osteoblastic differentiation functions. BMP signals mediated mostly by Smad transduced integrins activate focal kinase (FAK) its downstream molecules. This study was undertaken clarify how extracellular matrix converge with actions. We show that integrin activation involved in because disruption of either synthesis or collagen-α2β1-integrin binding inhibited the...
Histological analyses showed that expression of the parathyroid calcium-sensing receptor (CaSR) is decreased in adenomas. Because reduced CaSR may result insufficient suppression hormone secretion, elucidation regulatory mechanisms indispensable for understanding pathogenesis Two cDNA clones human with different 5′-untranslated regions have been isolated. However, structure promoter region and production multiple mRNAs are unknown. We cloned by screening a genomic library. The gene has two...