title: Epiregulin is critical for the acinar cell regeneration of the submandibular gland in a mouse duct ligation model.
abstract: Acinar cell regeneration from tubular structures has been reported to occur in duct-deligated salivary glands. However, the detailed process of acinar cell regeneration has not been clarified. We have developed a mouse duct ligation model to clarify the mechanisms underlying acinar cell regeneration, and we analyzed the epidermal growth factor receptor (EGFR) and epidermal growth factor (EGF) ligands using the model. We studied these ligands expressions in the course of acinar cell regeneration using immunohistochemistry and RT-PCR methods. In the duct-ligated portion of the submandibular gland (SMG) that underwent atrophy, newly formed acinar cells were observed arising from the tubular structures after the release of the duct obstruction. The constitutive expression of EGFR was observed by immunohistochemistry in both the duct-ligated and duct-deligated animals as well as in normal controls. The EGFR phosphorylation detected on the tubular structures after duct ligation paralleled the acinar cell regeneration. RT-PCR showed an increase in the epiregulin and heparin-binding EGF levels from day 0 to day 3 after the release of the duct obstruction. The EGF level was increased only after day 7. In vitro, cultured cells isolated from ligated SMGs proliferated and produced EGF ligands following the addition of epiregulin to the culture medium. These findings suggest that the tubular structures localized in an atrophic gland are the source of acinar cell regeneration of the salivary gland. The induction of EGF ligands, in particular epiregulin, may play an important role in acinar cell regeneration in this model.
authors.affiliation: Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nagai
authors.forename: Hideo
authors.initials: H
authors.lastname: Arai
authors.forename: Michisato
authors.initials: M
authors.lastname: Okudera
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
authors.forename: Hidero
authors.initials: H
authors.lastname: Oki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komiyama
mesh_terms: D061354:Acinar Cells / Q000502:physiology*; D066258:Amphiregulin; D000818:Animals; D001284:Atrophy; D066259:Betacellulin / Q000032:analysis; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D066255:EGF Family of Proteins / Q000032:analysis; D004815:Epidermal Growth Factor / Q000032:analysis / Q000187:drug effects; D066261:Epigen / Q000032:analysis; D066260:Epiregulin / Q000032:analysis* / Q000494:pharmacology; D066246:ErbB Receptors / Q000032:analysis / Q000187:drug effects; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor / Q000032:analysis; D007610:Kallikreins / Q000032:analysis / Q000187:drug effects; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D019696:Peptidylprolyl Isomerase / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012038:Regeneration / Q000502:physiology*; D018987:Salivary Ducts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013363:Submandibular Gland / Q000378:metabolism* / Q000473:pathology; D013364:Submandibular Gland Diseases / Q000378:metabolism* / Q000473:pathology; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000187:drug effects
chemical_list: D066258:Amphiregulin; C587849:Areg protein, mouse; D066259:Betacellulin; C587852:Btc protein, mouse; D066255:EGF Family of Proteins; C587855:Epgn protein, mouse; D066261:Epigen; D066260:Epiregulin; C587881:Ereg protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D007610:Kallikreins; C053223:epidermal growth factor binding protein, mouse; D019696:Peptidylprolyl Isomerase
keywords: acinar cell; duct obstruction; epiregulin; hyposalivation; mouse; submandibular gland