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European Tissue Repair Society Focus Meeting
Tissue Repair, Contraction, and the Myofibroblast
Nyon, Switzerland
November 18–20, 2004
The following compilation of abstracts represents a partial list of submissions received for presentation at the meeting. Please note the abstracts are arranged in alphabetical order (by presenter's name). Communications by the invited speakers will be published in a book by Landes Bioscience.: TGF‐β1 Signaling is Regulated by Negative Feedback Mechanism of BMP‐7 in Fibrotic Kidneys of Hereditary Nephrotic Mice
Author(s) -
Anan S,
Goto Y,
YamaguchiYamada M,
Sakata C,
Manabe N
Publication year - 2005
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130117a.x
Subject(s) - fibrosis , extracellular matrix , pathology , nephrotic syndrome , myofibroblast , mesangium , medicine , biology , endocrinology , microbiology and biotechnology , glomerulonephritis , kidney
ICR‐derived strain with gulomerulonephrisis (ICGN) mouse derived from ICR mouse is a newly established mouse strain with hereditary nephrotic syndrome. The affected ICGN mice consistently show the clinical signs of nephrotic syndrome, developing various degrees. The lesions consist of thickened capillary basement membrane, enlarged mesangium without cellular proliferation, and tubulointerstitial fibrosis. Based on these histopathological findings and clinical biochemical data, ICGN strain mouse is considered to be a good experimental model for human idiopathic nephrotic syndrome. Extracellular matrix (ECM) components provide structural integrity to the tissues, and mediate regulation of cell growth, migration, differentiation, etc. The damaged cells have increased secretion of ECM components. This is a kind of self‐protecting reaction that is associated with healing process against injury. However, the hyperaccumulation of ECM components leads to fibrosis, a pathological phenomenon. Therefore, it is very important to make clearly the process of fibrosis in ICGN strain mouse. In this study, the expression and localization of transforming growth factor beta1 (TGF‐β1), TGF‐β1 type I receptor (TGFR1), and bone morphogenic protein (BMP)‐7, which regulate the signals of TGF‐β1 negatively, were investigated by using immunohistochemical staining and Western blotting. High expression levels of TGF‐β1 and TGFR1 were observed in tubular epithelial cells of middle stage‐ICGN mice as compared with those of control ICR mice. BMP‐7 was strongly expressed in tubular epithelium of ICR mice, but it decreased with the progression of renal disease in ICGN mice. Moreover, no localization of BMP‐7 in expanded tubular epithelial cells in ICGN mice was seen. These data suggest that the increase of TGF‐β1 and TGFR1 and the degradation of negative regulation of TGF‐β1 by BMP‐7 in middle and late stages of ICGN mice play an important role in renal fibrosis of ICGN mice. The present findings may contribute to elucidate the pathogenic mechanisms of human idiopathic nephrotic syndrome.