Project title
FGF23對急性腎損傷的保護作用
Internal ID
MOST107-2314-B002-026-MY3
Principal Investigator
Start Date
August 1, 2019
End Date
July 31, 2020
Investigators
Organizations
Partner Organizations
Protective Effect of Fgf23 against Acute Kidney Injury = FGF23對急性腎損傷的保護作用
Keywords
急性腎損傷
纖維母細胞生長因子23
缺血/再灌注損傷
Acute kidney injury
Fibroblast growth factor 23
Ischemia-reperfusion injury
Description
Fibroblast growth factor 23 (FGF23) is a hormone which is predominately produced in bone. The main physiological functions of FGF23 are to prevent renal phosphate reabsorption, active vitamin D3 production by the kidney, and decrease the parathyroid hormone (PTH) concentration in the blood. Recent evidences indicated that FGF23 rapidly increases after acute kidney injury (AKI), and can serve as a biomarker for subsequent AKI as well as adverse outcomes post-AKI. However, the biologic role for this finding is still unclear and requires further investigation. To explore the effect of increased FGF23 during AKI, we injected FGF23 recombinant protein into ischemia-reperfusion induced acute kidney injury (IR-AKI) mice. The preliminary results show that FGF23 could ameliorates kidney injury which induced by ischemia-reperfusion injury. Western blot results showed that activated Akt survival pathway was much greater in the kidney of FGF23-treated IR-AKI group than that in IR-AKI group. Proliferation marker PCNA and differentiation marker E-cadherin were also upregulated in IR-AKI mouse kidney after FGF23 pretreated. Activated Akt and PCNA overexpression were found in renal tubular epithelium by immunohistochemistry analysis. These results showed that FGF23 accelerates the process of tubular regeneration. Furthermore, FGF23 could prevent IR-induced cell death in the AKI mouse kidney by TUNEL assay. Taken together, our incredible results suggested that FGF23 seems to play a critical role in protection from IR-AKI. However, our preliminary results were obtained from a single exogenous FGF23-treated mouse model. Therefore, in this project, we will shed light on (1) The protective role of FGF23 in AKI using another three different FGF23 loss-of-function animal models and one FGF23 gain-of-function folic acid-induced AKI model. (2) The molecular mechanism underlying the protection of renal tubules by FGF23 using two in vivo models. (3) The identification of critical cell types and molecular mechanisms directly involved in the protection against AKI by FGF23. (4) The association between FGF23 and the prognosis of AKI in critical patients. This project will lead to breakthrough in our understanding of the link between FGF23 and AKI.