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Attenuation of renal fibrosis in mice due to lack of bombesin receptor‐activated protein homologue.
- Source :
- Clinical & Experimental Pharmacology & Physiology; Oct2024, Vol. 51 Issue 10, p1-16, 16p
- Publication Year :
- 2024
-
Abstract
- Bombesin receptor‐activated protein (BRAP), encoded by the C6orf89 gene in humans, is expressed in various cells with undefined functions. BC004004, the mouse homologue of C6orf89, has been shown to play a role in bleomycin‐induced pulmonary fibrosis through the use of a BC004004 gene knockout mouse (BC004004−/−). In this study, we investigated the potential involvement of BRAP in renal fibrosis using two mouse models: unilateral ureteral obstruction (UUO) and type 2 diabetes mellitus induced by combination of a high‐fat diet (HFD) and streptozocin (STZ). BRAP or its homologue was expressed in tubular epithelial cells (TECs) in the kidneys of patients with chronic kidney disease (CKD) and in BC004004+/+ mice. Compared to control mice, BC004004−/− mice exhibited attenuated renal injury and renal fibrosis after UUO or after HFD/STZ treatment. Immunohistochemistry and immunoblot analyses of the kidneys of BC004004+/+ mice after UUO surgery showed a more significant decrease in E‐cadherin expression and a more significant increase in both α smooth muscle actin (α‐SMA) and vimentin expression compared to BC004004−/− mice. Additionally, stimulation with transforming growth factor‐β1 (TGF‐β1) led to a more significant decrease in E‐cadherin expression and a more significant increase in α‐SMA and vimentin expression in isolated TECs from BC004004+/+ than in those from BC004004−/− mice. These results suggest that an enhanced epithelial‐mesenchymal transition (EMT) process occurred in TECs in BC004004+/+ mice during renal injury, which might contribute to renal fibrosis. The loss of the BRAP homologue in BC004004−/− mice suppressed EMT activation in kidneys and contributed to the suppression of fibrosis during renal injury. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03051870
- Volume :
- 51
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Pharmacology & Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 179608809
- Full Text :
- https://doi.org/10.1111/1440-1681.13916