alpha 2-Antiplasmin Is Associated with the Progression of Fibrosis

作者：Kanno Yosuke^*; Kawashita Eri; Minamida Misato; Kaneiwa Aki; Okada Kiyotaka; Ueshima Shigeru; Matsuo Osamu; Matsuno Hiroyuki

来源：American Journal Of Pathology, 2010, 176(1): 238-245.

DOI：10.2353/ajpath.2010.090150

Systemic sclerosis results in tissue fibrosis due to the activation of fibroblasts and the ensuing overproduction of the extracellular matrix. We previously reported that the absence of alpha 2-antiplasmin (alpha 2AP) attenuated the process of dermal fibrosis; however, the detailed mechanism of how alpha 2AP affects the progression of fibrosis remained unclear. The goal of the present study was to examine the role of alpha 2AP in fibrotic change. We observed significantly higher levels of alpha 2AP expression in the skin of bleomycin-injected systemic sclerosis model mice in comparison with the levels seen in control mice. We also demonstrated that alpha 2AP induced myofibroblast differentiation, and the absence of alpha 2AP attenuated the induction of myofibroblast differentiation. Moreover, we found that connective tissue growth factor induced the expression of alpha 2AP through both the extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways in fibroblasts. interestingly, alpha 2AP also induced transforming growth factor-beta expression through the same pathways, and the inhibition of ERK1/2 and JNK slowed the progression of bleomycin-induced fibrosis. Our findings suggest that alpha 2AP is associated with the progression of fibrosis, and regulation of alpha 2AP expression by the ERK1/2 and JNK pathways may be an effective antifibrotic therapy for the treatment of Systemic sclerosis. (Am J Pathol 2010, 176:238-245; DOI: 10.2353/ajpath.2010.090150)

• 出版日期2010-1