P311 promotes renal fibrosis via TGFβ1/Smad signaling

• Published in: Scientific reports 2015-11, Vol.5 (1), p.17032-17032, Article 17032
• Main Authors: Yao, Zhihui, Yang, Sisi, He, Weifeng, Li, Lian, Xu, Rui, Zhang, Xiaorong, Li, Haisheng, Zhan, Rixing, Sun, Wei, Tan, Jianglin, Zhou, Junyi, Luo, Gaoxing, Wu, Jun
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 13/95; 14/63; 38/77; 64/110; 692/308/1426; 692/699/1585/3182; 82/29; Actins - genetics; Actins - metabolism; Adult; Animals; Disease Models, Animal; Female; Fibrosis; Gene Expression; Gene Knockout Techniques; Humanities and Social Sciences; Humans; Immunohistochemistry; Kidney - metabolism; Kidney - pathology; Kidney Diseases - diagnosis; Kidney Diseases - genetics; Kidney Diseases - metabolism; Kidney Diseases - pathology; Macrophages - metabolism; Macrophages - pathology; Male; Mice; Mice, Knockout; Middle Aged; multidisciplinary; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Protein Transport; Science; Signal Transduction; Smad Proteins - metabolism; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep17032

P311, a gene that was identified in 1993, has been found to have diverse biological functions in processes such as cell proliferation, migration and differentiation. However, its role in fibrosis is unknown. We previously observed that P311 is highly expressed in skin hypertrophic scars. In this study, P311 over-expression was detected in a subset of tubular epithelial cells in clinical biopsy specimens of renal fibrosis; this over-expression, was found concurrent with α-smooth muscle actin (α-SMA) and transforming growth factor beta1 (TGFβ1) expression. Subsequently, these results were verified in a mouse experimental renal fibrosis model induced by unilateral ureteral obstruction. The interstitial deposition of collagen, α-SMA and TGF-β1 expression and macrophage infiltration were dramatically decreased when P311 was knocked out. Moreover, TGFβ/Smad signaling had a critical effect on the promotion of renal fibrosis by P311. In conclusion, this study demonstrate that P311 plays a key role in renal fibrosis via TGFβ1/Smad signaling, which could be a novel target for the management of renal fibrosis.