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

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 beta-estradiol 3-benzoate (EB), the incidence of lesions and histological scores of fibrosis were examined in conjunction with immunohistochemistry for alpha-smooth muscle actin (alpha-SMA), platelet-derived growth factor receptor-alpha (PDGFR alpha) and estrogen receptor-alpha (ER alpha). 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. alpha-SMA and PDGFRa were positively stained mainly in fibrotic/inflammatory islets, and the histological score of alpha-SMA in the fibrotic islet decreased age-dependently. Notably, alpha-SMA and PDGFRa were co-expressed in inflammatory islets with a high score at all ages. The positive index of ER alpha 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 alpha-SMA and PDGFRa 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 alpha-SMA-positive myofibroblasts were considered to contribute to the development of fibrosis. Strong PDGFR alpha 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. (DOI: 10.1293/tox.26.1; J Toxicol Pathol 2013; 26: 1-10)