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Nitta Kosaku
Department Other, Other Position |
|
| Article types | Original article |
| Language | English |
| Peer review | Non peer reviewed |
| Title | Fibulin7 aggravates calcium oxalate-induced acute kidney injury by binding to calcium oxalate crystals. |
| Journal | Formal name：Journal of cellular physiology Abbreviation：J Cell Physiol ISSN code：10974652/00219541 |
| Volume, Issue, Page | 238(1),pp.165-178 |
| Author and coauthor | Sugiura Hidekazu, Tsunezumi Jun, Yanagisawa Hiromi, Futaya Mayuko, Nitta Kosaku, Tsuchiya Ken |
| Publication date | 2023/01 |
| Summary | Fibulin7 (Fbln7) is a matricellular protein that is structurally similar to short fibulins but does not possess elastogenic abilities. Fbln7 is localized on the cell surface of the renal tubular epithelium in the adult kidney. We previously reported that Fbln7 binds artificial calcium phosphate particles in vitro, and that heparin counteracts this binding by releasing Fbln7 from the cell surface. Fbln7 gene (Fbln7) deletion in vivo decreased interstitial fibrosis and improved renal function in a high phosphate diet-induced chronic kidney disease mouse model. However, the contribution of Fbln7 during acute injury response remains largely unknown. We hypothesized that Fbln7 serves as an exacerbating factor in acute kidney injury (AKI). We employed three AKI models in vivo and in vitro, including unilateral ureteral obstruction (UUO), cisplatin-induced AKI, and calcium oxalate (CaOx)-induced AKI. Here, we report that Fbln7KO mice were protected from kidney damage in a CaOx-induced AKI model. Using HEK293T cells, we found that Fbln7 overexpression enhanced the CaOx-induced upregulation of EGR1 and LAMB3, and that heparin treatment canceled this effect. Interestingly, the protective function observed in Fbln7KO kidneys was limited to the CaOx-induced AKI model, while Fbln7KO mice were not protected against UUO-induced renal fibrosis or cisplatin-induced renal tubular damage. Taken together, our study indicates that Fbln7 mediates the local deposition of CaOx and damages the renal tubular epithelium. Releasing Fbln7 from the cell surface via heparin/heparin derivatives or Fbln7 inhibitory antibodies may provide a general strategy to mitigate calcium crystal-induced kidney injuries. |
| DOI | 10.1002/jcp.30914 |
| PMID | 36370444 |