+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn

+ Translate
+ Recently Requested

Restoration of the mucous phenotype by retinoic acid in retinoid-deficient human bronchial cell cultures: changes in mucin gene expression



Restoration of the mucous phenotype by retinoic acid in retinoid-deficient human bronchial cell cultures: changes in mucin gene expression



American Journal of Respiratory Cell and Molecular Biology 20(1): 43-52



Retinoid-deficient cultures of airway epithelial cells undergo squamous differentiation. Treatment of such cultures with retinoic acid (RA) leads to restoration of the mucous phenotype. The purpose of our study was to characterize the cellular and molecular changes following RA treatment of retinoid-deficient human tracheobronchial epithelial cell cultures. Of particular interest was to determine when during the conversion of the squamous to the mucous phenotype the mucin genes MUC2, MUC5AC, and MUC5B were expressed. We used cornifin alpha and secreted mucin as markers to monitor the squamous and mucous phenotypes, respectively. Our studies showed that the RA responsiveness of the cultures progressively decreased with protracted retinoid deficiency, requiring higher RA concentrations to restore the mucous phenotype. Within 12 h after the start of RA treatment, cornifin alpha expression decreased, signaling the beginning of a change in cellular phenotype. At 24 h after addition of RA to the cultures, a significant number of mucous cells appeared, and at 72 h mucin was secreted in measurable amounts. Induction of mucin gene expression occurred sequentially: MUC2, MUC5AC, and MUC5B mRNAs were upregulated at 24, 48, and 72 h, respectively. When cultures maintained in 10(-8) M RA were treated with 10(-6) M RA, MUC2 but not MUC5AC and MUC5B mRNA levels were upregulated within 6 h. Our study indicates that MUC2 mRNA is an early marker of mucous differentiation, whereas MUC5AC and MUC5B mRNAs are expressed during more advanced stages of mucous differentiation. Our studies further suggest that each of the mucin genes is regulated by distinct mechanisms.

(PDF emailed within 0-6 h: $19.90)

Accession: 011294784

Download citation: RISBibTeXText

PMID: 9870916

DOI: 10.1165/ajrcmb.20.1.3310



Related references

Role of retinoid receptors in the regulation of mucin gene expression by retinoic acid in human tracheobronchial epithelial cells. Biochemical Journal 338: 351-357, 1999

Variation of human mucin gene expression in gastric cancer cell lines and gastric mucous cell primary cultures. European Journal of Cell Biology 78(11): 832-841, 1999

Retinoic acid induction of human cellular retinoic acid binding protein-II gene transcription is mediated by retinoic acid and retinoid X receptor heterodimers bound to one far upstream retinoic acid responsive element. Journal of Investigative Dermatology 102(4): 524, 1994

Retinoic acid induction of human cellular retinoic acid-binding protein-II gene transcription is mediated by retinoic acid receptor-retinoid X receptor heterodimers bound to one far upstream retinoic acid-responsive element with 5-base pair spacing. Journal of Biological Chemistry 269(35): 22334-9, 1994

The effect of 9-cis-retinoic acid on proliferation and differentiation of a spermatogonia and retinoid receptor gene expression in the vitamin A-deficient mouse testis. Endocrinology 139(10): 4269-4276, 1998

Comparison of N-(4-hydroxyphenyl)retinamide and all-trans-retinoic acid in the regulation of retinoid receptor-mediated gene expression in human breast cancer cell lines. Cancer Research 56(5): 1056-1062, 1996

Comparison of N-(4-hydroxyphenyl) retinamide and all-trans-retinoic acid in regulation of retinoid receptor-mediated gene expression in human breast cancer cell lines. Cancer Research 56(5): 1056-1062, 1996

Retinoic acid receptor and retinoid X receptor expression in retinoic acid-resistant human tumor cell lines. Molecular Carcinogenesis 8(2): 112-122, 1993

Novel retinoic acid, 9-CIS retinoic acid, in combination with all-trans retinoic acid is effective inducer of differentiation of retinoic acid resistant Hl 60 cells Relation to retinoic acid receptor and retinoid X receptor expression. Blood 82(10 SUPPL 1): 251A, 1993

9-cis retinoic acid--a better retinoid for the modulation of differentiation, proliferation and gene expression in human neuroblastoma. Journal of Neuro-Oncology 31(1-2): 85-91, 1997

Sp1 up-regulates cAMP-response-element-binding protein expression during retinoic acid-induced mucous differentiation of normal human bronchial epithelial cells. Biochemical Journal 410(1): 49-61, 2007

Expression of the retinoic acid nuclear receptors and retinoid X receptor gene in human breast cancer. Zhonghua Zhong Liu Za Zhi 17(6): 425-428, 1995

Effects of cyclic adenosine 3':5'-monophosphate-elevating agents and retinoic acid on differentiation in retinoid-deficient tracheal cultures. In Vitro Cellular & Developmental Biology 21(12): 688-692, 1985

Retinoic acid receptor gamma/retinoid X receptor alpha heterodimers bind to the retinoic acid response element in the promoter of the cellular retinol binding protein gene and induce its mRNA and protein expression in human epidermis in vivo. Journal of Investigative Dermatology 102(4): 625, 1994