title: The Process and Development Mechanism of Age-related Fibrosis in the Pancreatic Islets of Sprague-Dawley Rats: Immunohistochemical Detection of Myofibroblasts and Suppression Effect by Estrogen Treatment.
abstract: The mechanism of spontaneous islet fibrosis in Sprague-Dawley rats was investigated. Using sections of the pancreas in naive males aged 26 to 102 weeks old and 26-week-old males injected with β-estradiol 3-benzoate (EB), the incidence of lesions and histological scores of fibrosis were examined in conjunction with immunohistochemistry for α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-α (PDGFRα) and estrogen receptor-α (ERα). The incidence of islet fibrosis increased in 78-week-old animals compared to the 26-week-old animals, and the incidence of atrophy in the fibrotic islet increased in animals over 52 weeks old. α-SMA and PDGFRα were positively stained mainly in fibrotic/inflammatory islets, and the histological score of α-SMA in the fibrotic islet decreased age-dependently. Notably, α-SMA and PDGFRα were co-expressed in inflammatory islets with a high score at all ages. The positive index of ERα in the EB-treated group increased when compared with that of the naive group. However, it was independent of the existence of fibrosis. In contrast, the score of α-SMA and PDGFRα decreased in the EB-treated group. In conclusion, it was clarified that a part of age-related fibrosis in islets became atrophy with age, and α-SMA-positive myofibroblasts were considered to contribute to the development of fibrosis. Strong PDGFRα stainability in fibrotic/inflammatory islets may imply that myofibroblasts were stimulated by PDGF to produce an extracellular matrix. Although estradiol has been known to suppress fibrosis/inflammation in the islet, nuclear-located ER-dependent signaling was considered not to be involved in the suppression mechanism. EB possibly affected the inhibition of the appearance of myofibroblasts.
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Imaoka
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Jindo
authors.forename: Wataru
authors.initials: W
authors.lastname: Takasaki
keywords: Sprague-Dawley rat; fibrosis; myofibroblast; pancreatic islet; platelet-derived growth factor receptor-α; α-smooth muscle actin