scholarly journals Similarities in DSG1 and KRT3 Downregulation through Retinoic Acid Treatment and PAX6 Knockdown Related Expression Profiles: Does PAX6 Affect RA Signaling in Limbal Epithelial Cells?

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1651
Author(s):  
Lorenz Latta ◽  
Igor Knebel ◽  
Constanze Bleil ◽  
Tanja Stachon ◽  
Priya Katiyar ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cells ◽  
Receptor Antagonist ◽  
Mrna Expression ◽  
Retinoic Acid Receptor ◽  
Expression Profiles ◽  
Retinoid X Receptor ◽  
Elevated Concentration ◽  
Differentiation Markers ◽  
Altered Expression

Congenital PAX6-aniridia is a rare panocular disease resulting from limbal stem cell deficiency. In PAX6-aniridia, the downregulation of the retinol-metabolizing enzymes ADH7 (All-trans-retinol dehydrogenase 7) and ALDH1A1/A3 (Retinal dehydrogenase 1, Aldehyde dehydrogenase family 1 member A3) have been described in limbal epithelial cells (LECs) and conjunctival epithelial cells. The aim of this study was to identify the role of retinol derivates in the differentiation of human LEC and its potential impact on aniridia-associated keratopathy development. Human LEC were isolated from healthy donor corneas and were cultured with retinol, retinoic acid, or pan-retinoic acid receptor antagonist (AGN 193109) acting on RARα, β, γ (NR1B1, NR1B2 NR1B3) or were cultured with pan-retinoid X receptor antagonist (UVI 3003) acting on RXR α, β, γ (retinoid X receptor, NR2B1, NR2B2, BR2B3). Using qPCR, differentiation marker and retinoid-/fatty acid metabolism-related mRNA expression was analysed. DSG1 (Desmoglein 1), KRT3 (Keratin 3), and SPINK7 (Serine Peptidase Inhibitor Kazal Type 7) mRNA expression was downregulated when retinoid derivates were used. AGN 193109 treatment led to the upregulation of ADH7, KRT3, and DSG1 mRNA expression and to the downregulation of KRT12 (Keratin 12) and KRT19 (Keratin 19) mRNA expression. Retinol and all-trans retinoic acid affect some transcripts of corneal LEC in a similar way to what has been observed in the LEC of PAX6-aniridia patients with the altered expression of differentiation markers. An elevated concentration of retinol derivatives in LEC or an altered response to retinoids may contribute to this pattern. These initial findings help to explain ocular surface epithelia differentiation disorders in PAX6-aniridia and should be investigated in patient cells or in cell models in the future in more detail.

scholarly journals Retinoic Acid Receptor Isoform mRNA Expression Differs Between BCC and SCC of the Skin

2010 ◽  
Vol 146 (6) ◽  
Author(s):  
Fabian Hartmann ◽  
Maria Kosmidis ◽  
Beda Mühleisen ◽  
Lars E. French ◽  
Günther F. L. Hofbauer
Keyword(s):  
Retinoic Acid ◽  
Mrna Expression ◽  
Retinoic Acid Receptor ◽  
Acid Receptor

Ligand-inducible retinoid X receptor-mediated protein: DNA interactions in the retinoic acid receptor β2 gene promoter in vivo

1998 ◽  
Vol 136 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Masato Ikeda ◽  
Remco A Spanjaard ◽  
Elizabeth W Noordhoek ◽  
Akio Kawaguchi ◽  
Toshimasa Onaya ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Gene Promoter ◽  
Retinoid X Receptor ◽  
Dna Interactions ◽  
Acid Receptor ◽  
Protein Dna Interactions ◽  
Retinoic Acid Receptor Β2

AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1520-1531 ◽  
Author(s):  
M Gianni ◽  
M Li Calzi ◽  
M Terao ◽  
G Guiso ◽  
S Caccia ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Line ◽  
Acute Promyelocytic Leukemia ◽  
Retinoic Acid Receptor ◽  
Chromosomal Translocation ◽  
Promyelocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Stable Phase ◽  
Differentiation Markers

All-trans retinoic acid (ATRA) is successfully used in the cyto- differentiating treatment of acute promyelocytic leukemia (APL). Paradoxically, APL cells express PML-RAR, an aberrant form of the retinoic acid receptor type alpha (RAR alpha) derived from the leukemia- specific t(15;17) chromosomal translocation. We show here that AM580, a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist, is a powerful inducer of granulocytic maturation in NB4, an APL-derived cell line, and in freshly isolated APL blasts. After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor (G-CSF), the compound induces granulocytic maturation, as assessed by determination of the levels of leukocyte alkaline phosphatase, CD11b, CD33, and G-CSF receptor mRNA, at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects. By contrast, AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease. In NB4 cells, two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580, whereas RAR beta- or RAR gamma-specific ligands are totally ineffective. These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present. Binding experiments, using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha, show that AM580 has a lower affinity than ATRA for both receptors. However, in the presence of PML-RAR, the synthetic retinoid is a much better transactivator of retinoic acid-responsive element-containing promoters than the natural retinoid, whereas, in the presence of RAR alpha, AM580 and ATRA have similar activity. This may explain the strong cyto-differentiating potential of AM580 in PML-RAR-containing leukemic cells.

scholarly journals Altered expression of p63 isoforms and expansion of p63- and club cell secretory protein-positive epithelial cells in the lung as novel features of aging

2019 ◽  
Vol 316 (4) ◽  
pp. C492-C508 ◽  
Author(s):  
Jutaro Fukumoto ◽  
Sahebgowda Sidramagowda Patil ◽  
Sudarshan Krishnamurthy ◽  
Smita Saji ◽  
Irene John ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Protein Expression ◽  
Basal Cell ◽  
Expression Profiles ◽  
Type Ii ◽  
Cell Marker ◽  
Altered Expression ◽  
Club Cell ◽  
Protein Expression Profiles ◽  
Old Mice

Aging is a key contributor for subclinical progression of late-onset lung diseases. Basal, club, and type II alveolar epithelial cells (AECs) are lung epithelial progenitors whose capacities of differentiation are extensively studied. The timely transition of these cells in response to environmental changes helps maintain the intricate organization of lung structure. However, it remains unclear how aging affects their behavior. This paper demonstrates that the protein expression profiles of a type II AEC marker, prosurfactant protein C (pro-SPC), and a basal cell marker, p63, are altered in the lungs of 14-mo-old versus 7- to 9-wk-old mice. Expression of NH2-terminal-truncated forms of p63 (ΔNp63), a basal cell marker, and claudin-10, a club cell marker, in cytoplasmic extracts of lungs of 14-mo-old mice was upregulated. In contrast, nuclear expression of full-length forms of p63 (TAp63) decreases with age. These alterations in protein expression profiles coincide with dramatic changes in lung functions including compliance. Whole tissue lysates of middle-aged versus aged rhesus monkey lungs display similar age-associated alterations in pro-SPC expression. An age-associated decrease of TAp63 in nuclear lysates was observed in aged monkey group. Moreover, the lungs of 14-mo-old versus 7- to 9-wk-old mice display a wider spreading of ΔNp63-positive CCSP-positive bronchiolar epithelial cells. This expansion did not involve upregulation of Ki67, a representative proliferation marker. Collectively, it is postulated that 1) this expansion is secondary to a transition of progenitor cells committed to club cells from ΔNp63-negative to ΔNp63-positive status, and 2) high levels of cytoplasmic ΔNp63 expression trigger club cell migration.

scholarly journals Retinoic acid receptor α and retinoid-X receptor-specific agonists synergistically target telomerase expression and induce tumor cell death

Oncogene ◽  
2003 ◽  
Vol 22 (57) ◽  
pp. 9142-9150 ◽  
Author(s):  
Frédéric Pendino ◽  
Charles Dudognon ◽  
Francois Delhommeau ◽  
Tewfik Sahraoui ◽  
Maria Flexor ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Tumor Cell ◽  
Retinoic Acid Receptor ◽  
Retinoid X Receptor ◽  
Tumor Cell Death ◽  
Acid Receptor ◽  
Retinoic Acid Receptor Α
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