| Conditional overexpression of TGF-beta1 disrupts mouse salivary gland development and function. | |
| | |
MedLine Citation:
|
PMID: 20142803 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Transforming growth factor-beta (TGF-beta) signaling is known to affect salivary gland physiology by influencing branching morphogenesis, regulating ECM deposition, and controlling immune homeostasis. To study the role of TGF-beta1 in the salivary gland, we created a transgenic mouse (beta1(glo)) that conditionally overexpresses active TGF-beta1 upon genomic recombination by Cre recombinase. beta1(glo) mice were bred with an MMTV (mouse mammary tumor virus)-Cre (MC) transgenic line that expresses the Cre recombinase predominantly in the secretory cells of both the mammary and salivary glands. Although most of the double positive (beta1(glo)/MC) pups die either in utero or just after birth, clear defects in salivary gland morphogenesis such as reduced branching and increased mesenchyme could be seen. Those beta1(glo)/MC mice that survived into adulthood, however, had hyposalivation due to salivary gland fibrosis and acinar atrophy. Increased TGF-beta signaling was observed in the salivary gland with elevated phosphorylation of Smad2 and concomitant increase in ECM deposition. In particular, aberrant TGF-beta1 overexpression caused salivary gland hypofunction in this mouse model because of the replacement of normal glandular parenchyma with interstitial fibrous tissue. These results further implicate TGF-beta in pathological cases of salivary gland inflammation and fibrosis that occur with chronic infections in the glands or with the autoimmune disease, Sjögren's syndrome, or with radiation therapy given to head-and-neck cancer patients. |
| | |
Authors:
|
Bradford E Hall; Changyu Zheng; William D Swaim; Andrew Cho; Chandrasekharam N Nagineni; Michael A Eckhaus; Kathleen C Flanders; Indu S Ambudkar; Bruce J Baum; Ashok B Kulkarni |
Related Documents
:
|
11137033 - Receptor activator of nuclear factor kappa b ligand (rankl): another link between breas... 6873463 - Loss of differentiative potential of the mammary gland in ovariectomized mice: altered ... 9692223 - Tumor necrosis factor-alpha production enhancing activity of substituted 3'-methylthali... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Intramural Date: 2010-02-08 |
Journal Detail:
|
Title: Laboratory investigation; a journal of technical methods and pathology Volume: 90 ISSN: 1530-0307 ISO Abbreviation: Lab. Invest. Publication Date: 2010 Apr |
Date Detail:
|
Created Date: 2010-03-30 Completed Date: 2010-05-17 Revised Date: 2011-07-27 |
Medline Journal Info:
|
Nlm Unique ID: 0376617 Medline TA: Lab Invest Country: United States |
Other Details:
|
Languages: eng Pagination: 543-55 Citation Subset: IM |
Affiliation:
|
Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institutes of Health, Bethesda, MD 20892, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cells, Cultured Disease Models, Animal Fibrosis / physiopathology Inflammation / physiopathology Mice Mice, Transgenic Salivary Gland Diseases / physiopathology* Salivary Glands / growth & development*, pathology Transforming Growth Factor beta1 / physiology* Xerostomia / physiopathology* |
| Grant Support | |
ID/Acronym/Agency:
|
Z01 DE000723-01/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Transforming Growth Factor beta1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: 3D Telomere FISH defines LMP1-expressing Reed-Sternberg cells as end-stage cells with telomere-poor ...
Next Document: Hydrogen peroxide inhibits mTOR signaling by activation of AMPKalpha leading to apoptosis of neurona...