Members of the transforming growth factor-beta (TGF-beta) superfamily are critical regulators for epithelial growth and can alter the differentiation of keratinocytes. Transduction of TGF-beta signaling depends on the phosphorylation and activation of Smad proteins by heteromeric complexes of ligand-specific type I and II receptors. To understand the function of TGF-beta and activin-specific Smad, we generated transgenic mice that overexpress Smad2 in epidermis under the control of keratin 14 promoter. Overexpression of Smad2 increases endogenous Smad4 and TGF-beta 1 expression while heterozygous loss of Smad2 reduces their expression levels, suggesting a concerted action of Smad2 and -4 in regulating TGF-beta signaling during skin development. These transgenic mice have delayed hair growth, underdeveloped ears, and shorter tails. In their skin, there is severe thickening of the epidermis with disorganized epidermal architecture, indistinguishable basement membrane, and dermal fibrosis. These abnormal phenotypes are due to increased proliferation of the basal epidermal cells and abnormalities in the program of keratinocyte differentiation. The ectodermally derived enamel structure is also abnormal. Collectively, our study presents the first in vivo evidence that, by providing an auto-feedback in TGF-beta signaling, Smad2 plays a pivotal role in regulating TGF-beta-mediated epidermal homeostasis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1006/dbio.2001.0332 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Intervention of a Communication Between PI3K/Akt and β-Catenin by (-)-Epigallocatechin-3-Gallate Suppresses TGF-β1-Promoted Epithelial-Mesenchymal Transition and Invasive Phenotype of NSCLC Cells.
Environ Toxicol
January 2025
Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
The epithelial-mesenchymal transition (EMT) assists in the acquisition of invasiveness, relapse, and resistance in non-small cell lung cancer (NSCLC) and can be caused by the signaling of transforming growth factor-β1 (TGF-β1) through Smad-mediated or Smad-independent pathways. (-)-Epigallocatechin-3-gallate (EGCG), a multifunctional cancer-preventing bioconstituent found in tea polyphenols, has been shown to repress TGF-β1-triggered EMT in the human NSCLC A549 cell line by inhibiting the activation of Smad2 and Erk1/2 or reducing the acetylation of Smad2 and Smad3. However, its impact on the Smad-independent pathway remains unclear.
View Article and Find Full Text PDFInvolvement of TGF-β, mTOR, and inflammatory mediators in aging alterations during myxomatous mitral valve disease in a canine model.
Geroscience
January 2025
Department for Basic and Preclinical Sciences, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Torun, 87-100, Torun, Poland.
Inflammaging, a state of chronic low-grade inflammation associated with aging, has been linked to the development and progression of various disorders. Cellular senescence, a state of irreversible growth arrest, is another characteristic of aging that contributes to the pathogenesis of cardiovascular pathology. Senescent cells accumulate in tissues over time and secrete many inflammatory mediators, further exacerbating the inflammatory environment.
View Article and Find Full Text PDFFOXS1, frequently inactivated by promoter methylation, inhibited colorectal cancer cell growth by promoting TGFBI degradation through autophagy-lysosome pathway.
J Adv Res
January 2025
Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016 Zhejiang, China; Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016 Zhejiang, China. Electronic address:
Introduction: Tumor suppressor gene (TSG) inactivation by epigenetic modifications contributes to the carcinogenesis and progression of colorectal cancer (CRC). Expression profiling and CpG methylomics revealed that a forkhead-box transcriptional factor, FOXS1, is downregulated and methylated in CRC.
Objectives: To assess the biological functions and underlying mechanisms of FOXS1 in colorectal cancer.
Cyclooxygenase 2 overexpression suppresses Smad3 and augments ERK1/2 signaling activated by TGFβ1 in endometrial stromal cells: a novel insight into endometriosis pathogenesis.
Mol Cell Endocrinol
January 2025
The Gynecology Department, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address:
Research Question: To investigate the underlying mechanisms driving the opposing effects of transforming growth factor-beta 1 (TGFβ1) on the proliferation of control (CESCs) and ectopic (EESCs) endometrial stromal cells.
Design: Cell proliferation assays (CCK-8 and colony formation) were employed to assess the effects of TGFβ1 on CESC and EESC proliferation. An immortalized human endometrial stromal cell line (HESC) was used to elucidate the mechanisms behind cytostatic effect of TGFβ1 and the potential role of cyclooxygenase (COX)-2 in mediating the modulation of TGFβ1 signaling.
Callistephus A from Callistephus chinensis Nees alleviates concanavalin A-induced immunological liver injury in mice by inhibiting the activation of JAK/STAT1 and MAPK signaling pathways.
Int Immunopharmacol
January 2025
School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:
Callistephus chinensis Nees is an herbaceous plant in the Asteraceae family that has various traditional effects, especially in preventing liver disease. Callistephus A (CA) is a sesquiterpene compound with a rare 6/7 ring skeleton, which has been isolated only from the Callistephus chinensis Nees, but whether CA protects the liver is unknown. Immunological liver injury (ILI) is a common liver disease mediated by the immune system.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!