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2018 ; 131
(5
): 532-538
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Protection Effect of Exogenous Fibroblast Growth Factor 21 on the Kidney Injury
in Vascular Calcification Rats
#MMPMID29483386
Shi YC
; Lu WW
; Hou YL
; Fu K
; Gan F
; Cheng SJ
; Wang SP
; Qi YF
; Liu JH
Chin Med J (Engl)
2018[Mar]; 131
(5
): 532-538
PMID29483386
show ga
BACKGROUND: Chronic kidney disease (CKD) is closely related to the cardiovascular
events in vascular calcification (VC). However, little has known about the
characteristics of kidney injury caused by VC. Fibroblast growth factor 21
(FGF21) is an endocrine factor, which takes part in various metabolic actions
with the potential to alleviate metabolic disorder diseases. Even FGF21 has been
regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear.
Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats.
METHODS: The male Sprague-Dawley rats were divided into three groups: (1) control
group, (2) Vitamin D3 plus nicotine (VDN)-induced VC group, (3) FGF21-treated VDN
group. After 4 weeks, the rats were killed and the blood was collected for serum
creatinine, urea nitrogen, calcium, and phosphate measurement. Moreover, the
renal tissues were homogenized for alkaline phosphatases (ALPs) activity and
calcium content. The levels of FGF21 protein were measured by radioimmunoassay.
The levels of ?-Klotho and FGF receptor 1 (FGFR1) protein were measured by
enzyme-linked immunosorbent assay (ELISA). The structural damage and
calcifications in aortas were stained by Alizarin-red S. Moreover, the structure
of kidney was observed by hematoxylin and eosin staining. RESULTS: The renal
function impairment caused by VDN modeling was ameliorated by FGF21 treatment,
inhibited the elevated serum creatinine and urea level by 20.5% (34.750 ± 4.334
?mol/L vs. 27.630 ± 2.387 ?mol/L) and 4.0% (7.038 ± 0.590 mmol/L vs. 6.763 ±
0.374 mmol/L; P < 0.01), respectively, together with the structural damages of
glomerular atrophy and renal interstitial fibrosis. FGF21 treatment downregulated
the ALP activity, calcium content in the kidney of VC rats by 42.1% (P < 0.01)
and 11.7% (P < 0.05) as well as ameliorated the aortic injury and calcification
as compared with VDN treatment alone group, indicating an ameliorative effect on
VC. ELISA assays showed that the expression of ?-Klotho, a component of FGF21
receptor system, was increased in VDN-treated VC rats by 37.4% (6.588 ± 0.957
pg/mg vs. 9.054 ± 0.963 pg/mg; P < 0.01), indicating an FGF21-resistant state.
Moreover, FGF21 treatment downregulated the level of ?-Klotho in renal tissue by
16.7% (9.054 ± 0.963 pg/mg vs. 7.544 ± 1.362 pg/mg; P < 0.05). However, the level
of FGFR1, the receptor of FGF21, kept unchanged under VDN and VDN plus FGF21
administration (0.191 ± 0.0376 ng/mg vs. 0.189 ± 0.032 ng/mg vs. 0.181 ± 0.034
ng/mg; P > 0.05). CONCLUSIONS: In the present study, FGF21 was observed to
ameliorate the kidney injury in VDN-induced VC rats. FGF21 might be a potential
therapeutic factor in CKD by cutting off the vicious circle between VC and kidney
injury.
|Animals
[MESH]
|Calcium/metabolism
[MESH]
|Fibroblast Growth Factors/pharmacology/*therapeutic use
[MESH]