Mitogen-activated protein kinase up-regulation and activation during rat parotid gland atrophy and regeneration: Role of epidermal growth factor and β2-adrenergic receptors

Howard Dang, James J. Elliott, Alan L. Lin, Bing Zhu, Michael S. Katz, Chih-ko Yeh

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The rat secretory ductal obstruction model has been widely used to assess salivary gland injury, growth, and differentiation. In this study, a novel ductal obstruction and release procedure was used to explore the signaling pathways leading to salivary gland regeneration. Rats underwent bilateral parotid ductal obstruction in which the duct was occluded against a plastic disk subcutaneously and released by external ligature removal. This ductal obstruction/release procedure was validated to produce glandular atrophy and regeneration with histological analysis and periodic acid-Schiff staining. Immunoblot analysis indicated that during ductal obstruction and the early post-release period (day 7), expression of immunoreactive proliferating cell nuclear antigen and vimentin was increased in the parotid glands compared with sham-operated animals. Immunohistochemical staining and immunoblots revealed up-regulation of the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated receptor kinase (ERK)1/2, and p38 during the atrophic and regeneration phases of ductal obstruction/release. Similarly, increases in activated, i.e., phosphorylated, ERK1/2 (pERK1/2) and p38 (phospho-p38) were demonstrable in both ductal and recovering acinar cells, with pERKs expressed predominantly in the nuclei and phospho-p38 distributed throughout the cells. Furthermore, levels of epidermal growth factor (EGF) receptor and β2-adrenergic receptor (β2-AR) were elevated in the ligated glands and at day 7 post-release; β1-AR levels did not change over the same time period. These results support the view that cell proliferation is involved in duct ligation-induced atrophy of the rat parotid gland and gland recovery upon ligature removal. Up-regulation of ERKs and p38, and the activation of these MAPKs by up-regulated EGF and β2-ARs, may be important signaling components underlying glandular atrophy and subsequent regeneration.

Original languageEnglish (US)
Pages (from-to)546-557
Number of pages12
JournalDifferentiation
Volume76
Issue number5
DOIs
StatePublished - Jun 2008

Fingerprint

Parotid Gland
Mitogen-Activated Protein Kinases
Epidermal Growth Factor
Adrenergic Receptors
Atrophy
Regeneration
Up-Regulation
Ligation
Salivary Glands
Staining and Labeling
Periodic Acid
Acinar Cells
Extracellular Signal-Regulated MAP Kinases
Proliferating Cell Nuclear Antigen
p38 Mitogen-Activated Protein Kinases
Vimentin
Epidermal Growth Factor Receptor
Plastics
Cell Proliferation
Wounds and Injuries

Keywords

  • Extracellular signal-regulated kinase
  • p38
  • Salivary gland
  • Tissue regeneration

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Mitogen-activated protein kinase up-regulation and activation during rat parotid gland atrophy and regeneration : Role of epidermal growth factor and β2-adrenergic receptors. / Dang, Howard; Elliott, James J.; Lin, Alan L.; Zhu, Bing; Katz, Michael S.; Yeh, Chih-ko.

In: Differentiation, Vol. 76, No. 5, 06.2008, p. 546-557.

Research output: Contribution to journalArticle

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