Vitamin A deficiency and inflammation: the pivotal role of secretory cells in the development of atrophic, hyperplastic and metaplastic change in the tracheal epithelium in vivo

Although the epithelial lining of much of the mammalian urinary tract is known simply as the urothelium, this epithelium can be divided into at least three lineages of renal pelvis/ureter, bladder/trigone, and proximal urethra based on their embryonic origin, uroplakin content, keratin expression pattern, in vitro growth potential, and propensity to keratinize during vitamin A deficiency. Moreover, these cells remain phenotypically distinct even after they have been serially passaged under identical culture conditions, thus ruling out local mesenchymal influence as the sole cause of their in vivo differences. During vitamin A deficiency, mouse urothelium form multiple keratinized foci in proximal urethra probably originating from scattered K14-positive basal cells, and the keratinized epithelium expands horizontally to replace the surrounding normal urothelium. These data suggest that the urothelium consists of multiple cell lineages, that trigone urothelium is closely related to the urothelium covering the rest of the bladder, and that lineage heterogeneity coupled with cell migration/replacement form the cellular basis for urothelial squamous metaplasia.

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Genotype Effects on β-Carotene Conversion to Vitamin A: Implications on Reducing Vitamin A Deficiency in the Philippines

Food and Nutrition Bulletin ◽

10.1177/03795721211060229 ◽

2021 ◽

pp. 037957212110602

Author(s):

Mark Pretzel P. Zumaraga ◽

Jose Maria Reynaldo Apollo Arquiza ◽

Mae Anne Concepcion ◽

Leah Perlas ◽

Ma. Neda Alcudia-Catalma ◽

...

Keyword(s):

Vitamin A ◽

Children And Adolescents ◽

Vitamin A Deficiency ◽

The Philippines ◽

Fisher Exact Test ◽

National Capital Region ◽

Nutrition Survey ◽

Vitamin A Status ◽

Genotype Frequencies

Background: The study aimed to identify two beta-carotene 15,15′-monooxygenase (BCMO1) mutations, namely R267S and A379V, and determine their association with vitamin A status among Filipinos 6 to 19 years old respondents of the 2013 Philippine National Nutrition Survey living in the National Capital Region. Materials and Methods: This study followed cross-sectional design. Whole blood specimen was collected in the morning and was used as source of genomic DNA and serum for retinol concentration determination. Fisher exact test was performed to determine whether genotype frequencies were associated to retinol concentrations/vitamin A deficiency status. A level of P < .05 was identified as significant. Results: A total of 693 Filipino children and adolescents were included. Of the 693, there were at least 7.6% who bears the combined mutations for R267S + A379V. Association analysis showed that an inverse relationship exists between the A379V TT variant and vitamin A status. Although the exact role of these identified polymorphisms on retinol/carotenoid metabolism need to be confirmed in dedicated functional studies. Conclusion: This study has identified for the first time the presence of 2 nonsynonymous genetic variants/mutations in the coding region of BCMO1 gene. Interestingly, one of these two variants, the A379V T, was found to be associated with vitamin A status. It is, therefore, warranted to investigate the role of BCMO1 variants for the success of supplementation programs and fortification efforts among vulnerable populations in this region. Genetic variability should be considered for future provitamin A supplementation recommendations among children and adolescents in the Philippines.

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Complex regulation of TGF beta expression by retinoic acid in the vitamin A-deficient rat

Development ◽

10.1242/dev.111.4.1081 ◽

1991 ◽

Vol 111 (4) ◽

pp. 1081-1086 ◽

Cited By ~ 2

Author(s):

A.B. Glick ◽

B.K. McCune ◽

N. Abdulkarem ◽

K.C. Flanders ◽

J.A. Lumadue ◽

...

Keyword(s):

Retinoic Acid ◽

Vitamin A ◽

Vitamin A Deficiency ◽

Alveolar Epithelium ◽

Tgf Beta ◽

Basal Expression ◽

Beta 2 ◽

Complex Regulation ◽

First Time

We report the results of a histochemical study, using polyclonal antipeptide antibodies to the different TGF beta isoforms, which demonstrates that retinoic acid regulates the expression of TGF beta 2 in the vitamin A-deficient rat. Basal expression of TGF beta 2 diminished under conditions of vitamin A deficiency. Treatment with retinoic acid caused a rapid and transient induction of TGF beta 2 and TGF beta 3 in the epidermis, tracheobronchial and alveolar epithelium, and intestinal mucosa. Induction of TGF beta 1 expression was also observed in the epidermis. In contrast to these epithelia, expression of the three TGF beta isoforms increased in vaginal epithelium during vitamin A deficiency, and decreased following systemic administration of retinoic acid. Our results show for the first time the widespread regulation of TGF beta expression by retinoic acid in vivo, and suggest a possible mechanism by which retinoics regulate the functions of both normal and pre-neoplastic epithelia.

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Surface Morphology of Tracheal Epithelium in Vitamin A Deficiency and Reversal

Experimental Lung Cancer ◽

10.1007/978-3-642-61939-7_24 ◽

1974 ◽

pp. 257-264 ◽

Cited By ~ 9

Author(s):

Curtis D. Port ◽

David W. Baxter ◽

Curtis C. Harris

Keyword(s):

Vitamin A ◽

Surface Morphology ◽

Vitamin A Deficiency ◽

Tracheal Epithelium

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Pivotal role of STIM2, but not STIM1, in IL-4 production by IL-3–stimulated murine basophils

Science Signaling ◽

10.1126/scisignal.aav2060 ◽

2019 ◽

Vol 12 (576) ◽

pp. eaav2060 ◽

Cited By ~ 1

Author(s):

Soichiro Yoshikawa ◽

Masatsugu Oh-hora ◽

Ryota Hashimoto ◽

Toshihisa Nagao ◽

Louis Peters ◽

...

Keyword(s):

Immune Responses ◽

Immune Complexes ◽

Immunoglobulin E ◽

Allergic Inflammation ◽

Vital Role ◽

Basophil Activation ◽

Pivotal Role ◽

Time Courses

Basophils have nonredundant roles in various immune responses that require Ca2+influx. Here, we examined the role of two Ca2+sensors, stromal interaction molecule 1 and 2 (STIM1 and STIM2), in basophil activation. We found that loss of STIM1, but not STIM2, impaired basophil IL-4 production after stimulation with immunoglobulin E (IgE)–containing immune complexes. In contrast, when basophils were stimulated with IL-3, loss of STIM2, but not STIM1, reduced basophil IL-4 production. This difference in STIM proteins was associated with distinct time courses of Ca2+influx and transcription of theIl4gene that were elicited by each stimulus. Similarly, basophil-specific STIM1 expression was required for IgE-driven chronic allergic inflammation in vivo, whereas STIM2 was required for IL-4 production after combined IL-3 and IL-33 treatment in mice. These data indicate that STIM1 and STIM2 have differential roles in the production of IL-4, which are stimulus dependent. Furthermore, these results illustrate the vital role of STIM2 in basophils, which is often considered to be less important than STIM1.

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CMO1 Deficiency Abolishes Vitamin A Production from β-Carotene and Alters Lipid Metabolism in Mice

Journal of Biological Chemistry ◽

10.1074/jbc.m706763200 ◽

2007 ◽

Vol 282 (46) ◽

pp. 33553-33561 ◽

Cited By ~ 168

Author(s):

Susanne Hessel ◽

Anne Eichinger ◽

Andrea Isken ◽

Jaume Amengual ◽

Silke Hunzelmann ◽

...

Keyword(s):

Lipid Metabolism ◽

Vitamin A ◽

Vitamin A Deficiency ◽

Elevated Serum ◽

Pcr Analysis ◽

Marker Genes ◽

Mouse Mutant ◽

Adipose Tissues ◽

Β Carotene

Carotenoids are currently investigated regarding their potential to lower the risk of chronic disease and to combat vitamin A deficiency in humans. These plant-derived compounds must be cleaved and metabolically converted by intrinsic carotenoid oxygenases to support the panoply of vitamin A-dependent physiological processes. Two different carotenoid-cleaving enzymes were identified in mammals, the classical carotenoid-15,15′-oxygenase (CMO1) and a putative carotenoid-9′,10′-oxygenase (CMO2). To analyze the role of CMO1 in mammalian physiology, here we disrupted the corresponding gene by targeted homologous recombination in mice. On a diet providing β-carotene as major vitamin A precursor, vitamin A levels fell dramatically in several tissues examined. Instead, this mouse mutant accumulated the provitamin in large quantities (e.g. as seen by an orange coloring of adipose tissues). Besides impairments in β-carotene metabolism, CMO1 deficiency more generally interfered with lipid homeostasis. Even on a vitamin A-sufficient chow, CMO1-/- mice developed a fatty liver and displayed altered serum lipid levels with elevated serum unesterified fatty acids. Additionally, this mouse mutant was more susceptible to high fat diet-induced impairments in fatty acid metabolism. Quantitative reverse transcription-PCR analysis revealed that the expression of peroxisome proliferator-activated receptor γ-regulated marker genes related to adipogenesis was elevated in visceral adipose tissues. Thus, our study identifies CMO1 as the key enzyme for vitamin A production and provides evidence for a role of carotenoids as more general regulators of lipid metabolism.

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Migration, Marital Status and Smoking as Risk Determinants of Cancer

Scandinavian Journal of Social Medicine ◽

10.1177/140349488701500203 ◽

1987 ◽

Vol 15 (2) ◽

pp. 67-72 ◽

Cited By ~ 10

Author(s):

Leena Tenkanen ◽

Lyly Teppo

Keyword(s):

Risk Factors ◽

Lung Cancer ◽

High Risk ◽

Vitamin A ◽

Marital Status ◽

Psychosocial Stress ◽

Vitamin A Deficiency ◽

Cancer Epidemiology ◽

Risk Determinants

To study the importance of migration to urban area, marital status and smoking as risk factors in cancer, a cohort of 4475 Finnish men was followed up for the occurrence of cancer during the period 1964–1980. Of particular interest was the interaction of migration or marital status with smoking. For cancers at all sites, not married urbanized smoking men had the greatest risk, followed by not married native urban smokers. This pattern was mainly due to high risk of cancers of the lung and larynx among the urbanized men, with a risk peak among urbanized not married smokers. The pattern persisted even when the amount smoked was allowed for. The importance in lung cancer epidemiology of vitamin A deficiency, occupation and psychosocial stress was discussed, and some support was found for the role of psychosocial stress in both the migration and the marital status factors.

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