Role for Notch signaling in salivary acinar cell growth and differentiation

Howard Dang, Alan L. Lin, Binxian Zhang, Hong Mei Zhang, Michael S. Katz, Chih-ko Yeh

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. The Notch signaling is essential for Drosophila salivary gland development but its role in mammalian salivary gland remains unclear. The human salivary epithelial cell line, HSG, was studied to determine the role of Notch signaling in salivary epithelial cell differentiation. HSG expressed Notch 1 to 4, and the Notch ligands Jagged 1 and 2 and Delta 1. Treatment of HSG cells with inhibitors of γ-secretase, which is required for Notch cleavage and activation, blocked vimentin and cystatin S expression, an indicator of HSG differentiation. HSG differentiation was also associated with Notch downstream signal Hes-1 expression, and Hes-1 expression was inhibited by γ-secretase inhibitors. siRNA corresponding to Notch 1 to 4 was used to show that silencing of all four Notch receptors was required to inhibit HSG differentiation. Normal human submandibular gland expressed Notch 1 to 4, Jagged 1 and 2, and Delta 1, with nuclear localization indicating Notch signaling in vivo. Hes-1 was also expressed in the human tissue, with staining predominantly in the ductal cells. In salivary tissue from rats undergoing and recovering from ductal obstruction, we found that Notch receptors and ligands were expressed in the nucleus of the regenerating epithelial cells. Taken together, these data suggest that Notch signaling is critical for normal salivary gland cell growth and differentiation.

Original languageEnglish (US)
Pages (from-to)724-731
Number of pages8
JournalDevelopmental Dynamics
Volume238
Issue number3
DOIs
StatePublished - Mar 2009

Fingerprint

Acinar Cells
Salivary Glands
Notch Receptors
Cell Differentiation
Amyloid Precursor Protein Secretases
Epithelial Cells
Salivary Cystatins
Stem Cells
Growth
Ligands
Submandibular Gland
Vimentin
Small Interfering RNA
Drosophila
Maintenance
Staining and Labeling
Cell Line
Jagged-1 Protein

Keywords

  • Epithelial cell differentiation
  • Hes1
  • Notch
  • Salivary gland

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Role for Notch signaling in salivary acinar cell growth and differentiation. / Dang, Howard; Lin, Alan L.; Zhang, Binxian; Zhang, Hong Mei; Katz, Michael S.; Yeh, Chih-ko.

In: Developmental Dynamics, Vol. 238, No. 3, 03.2009, p. 724-731.

Research output: Contribution to journalArticle

Dang, Howard ; Lin, Alan L. ; Zhang, Binxian ; Zhang, Hong Mei ; Katz, Michael S. ; Yeh, Chih-ko. / Role for Notch signaling in salivary acinar cell growth and differentiation. In: Developmental Dynamics. 2009 ; Vol. 238, No. 3. pp. 724-731.
@article{13d8a1b03f924a36a95a41e9c9198048,
title = "Role for Notch signaling in salivary acinar cell growth and differentiation",
abstract = "The Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. The Notch signaling is essential for Drosophila salivary gland development but its role in mammalian salivary gland remains unclear. The human salivary epithelial cell line, HSG, was studied to determine the role of Notch signaling in salivary epithelial cell differentiation. HSG expressed Notch 1 to 4, and the Notch ligands Jagged 1 and 2 and Delta 1. Treatment of HSG cells with inhibitors of γ-secretase, which is required for Notch cleavage and activation, blocked vimentin and cystatin S expression, an indicator of HSG differentiation. HSG differentiation was also associated with Notch downstream signal Hes-1 expression, and Hes-1 expression was inhibited by γ-secretase inhibitors. siRNA corresponding to Notch 1 to 4 was used to show that silencing of all four Notch receptors was required to inhibit HSG differentiation. Normal human submandibular gland expressed Notch 1 to 4, Jagged 1 and 2, and Delta 1, with nuclear localization indicating Notch signaling in vivo. Hes-1 was also expressed in the human tissue, with staining predominantly in the ductal cells. In salivary tissue from rats undergoing and recovering from ductal obstruction, we found that Notch receptors and ligands were expressed in the nucleus of the regenerating epithelial cells. Taken together, these data suggest that Notch signaling is critical for normal salivary gland cell growth and differentiation.",
keywords = "Epithelial cell differentiation, Hes1, Notch, Salivary gland",
author = "Howard Dang and Lin, {Alan L.} and Binxian Zhang and Zhang, {Hong Mei} and Katz, {Michael S.} and Chih-ko Yeh",
year = "2009",
month = "3",
doi = "10.1002/dvdy.21875",
language = "English (US)",
volume = "238",
pages = "724--731",
journal = "Developmental Dynamics",
issn = "1058-8388",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Role for Notch signaling in salivary acinar cell growth and differentiation

AU - Dang, Howard

AU - Lin, Alan L.

AU - Zhang, Binxian

AU - Zhang, Hong Mei

AU - Katz, Michael S.

AU - Yeh, Chih-ko

PY - 2009/3

Y1 - 2009/3

N2 - The Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. The Notch signaling is essential for Drosophila salivary gland development but its role in mammalian salivary gland remains unclear. The human salivary epithelial cell line, HSG, was studied to determine the role of Notch signaling in salivary epithelial cell differentiation. HSG expressed Notch 1 to 4, and the Notch ligands Jagged 1 and 2 and Delta 1. Treatment of HSG cells with inhibitors of γ-secretase, which is required for Notch cleavage and activation, blocked vimentin and cystatin S expression, an indicator of HSG differentiation. HSG differentiation was also associated with Notch downstream signal Hes-1 expression, and Hes-1 expression was inhibited by γ-secretase inhibitors. siRNA corresponding to Notch 1 to 4 was used to show that silencing of all four Notch receptors was required to inhibit HSG differentiation. Normal human submandibular gland expressed Notch 1 to 4, Jagged 1 and 2, and Delta 1, with nuclear localization indicating Notch signaling in vivo. Hes-1 was also expressed in the human tissue, with staining predominantly in the ductal cells. In salivary tissue from rats undergoing and recovering from ductal obstruction, we found that Notch receptors and ligands were expressed in the nucleus of the regenerating epithelial cells. Taken together, these data suggest that Notch signaling is critical for normal salivary gland cell growth and differentiation.

AB - The Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. The Notch signaling is essential for Drosophila salivary gland development but its role in mammalian salivary gland remains unclear. The human salivary epithelial cell line, HSG, was studied to determine the role of Notch signaling in salivary epithelial cell differentiation. HSG expressed Notch 1 to 4, and the Notch ligands Jagged 1 and 2 and Delta 1. Treatment of HSG cells with inhibitors of γ-secretase, which is required for Notch cleavage and activation, blocked vimentin and cystatin S expression, an indicator of HSG differentiation. HSG differentiation was also associated with Notch downstream signal Hes-1 expression, and Hes-1 expression was inhibited by γ-secretase inhibitors. siRNA corresponding to Notch 1 to 4 was used to show that silencing of all four Notch receptors was required to inhibit HSG differentiation. Normal human submandibular gland expressed Notch 1 to 4, Jagged 1 and 2, and Delta 1, with nuclear localization indicating Notch signaling in vivo. Hes-1 was also expressed in the human tissue, with staining predominantly in the ductal cells. In salivary tissue from rats undergoing and recovering from ductal obstruction, we found that Notch receptors and ligands were expressed in the nucleus of the regenerating epithelial cells. Taken together, these data suggest that Notch signaling is critical for normal salivary gland cell growth and differentiation.

KW - Epithelial cell differentiation

KW - Hes1

KW - Notch

KW - Salivary gland

UR - http://www.scopus.com/inward/record.url?scp=61649102424&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61649102424&partnerID=8YFLogxK

U2 - 10.1002/dvdy.21875

DO - 10.1002/dvdy.21875

M3 - Article

VL - 238

SP - 724

EP - 731

JO - Developmental Dynamics

JF - Developmental Dynamics

SN - 1058-8388

IS - 3

ER -