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2015 ; 16
(ä): 169
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Intermedin protects against renal ischemia-reperfusion injury by inhibiting
endoplasmic reticulum stress
#MMPMID26498843
Wang Y
; Tian J
; Qiao X
; Su X
; Mi Y
; Zhang R
; Li R
BMC Nephrol
2015[Oct]; 16
(ä): 169
PMID26498843
show ga
BACKGROUND: Intermedin (IMD) is a novel member of the calcitonin/calcitonin
gene-related peptide family. Endoplasmic reticulum stress (ERS) has been
implicated in the pathology of renal ischemia/reperfusion (IRI). In the present
study, we investigated whether IMD could reduce ERS damage after renal ischemia.
METHODS: The kidneys of SD rats were subjected to 45 min of warm ischemia
followed by 24 h of reperfusion. The hypoxia/reoxygenation(H/R) model in NRK-52E
cells consisted of hypoxia for 1 h and reoxygenation for 2 h. IMD was
over-expressed in vivo and in vitro using the vector pcDNA3.1-IMD. The serum
creatinine concentration and lactate dehydrogenase (LDH) activity in the plasma
were determined. Histologic examinations of renal tissues were performed with PAS
staining. Real-time PCR and Western blotting were used to determine the mRNA and
protein levels, respectively. Additionally, ER staining was used to detect the
ERS response. RESULTS: In the rat renal IRI model, we found that IMD gene
transfer markedly improved renal function and pathology and decreased LDH
activity and cell apoptosis compared with the kidneys that were transfected with
the control plasmid. IMD significantly attenuated the ERS stress parameters
compared with IRI group. Indeed, IMD down-regulated glucose-regulated protein 78
(GRP78), C/EBP homologous protein(CHOP), and caspase 12 protein and mRNA levels.
Moreover, in the NRK-52E cell H/R model, IMD overexpression prevented the
apoptosis induced by H/R. Furthermore, IMD ameliorated the ER structural changes
and concomitantly decreased the levels of GRP78, CHOP and caspase-12. CONCLUSION:
This study revealed that IMD protects against renal IRI by suppressing ERS and
ERS-related apoptosis.
|*Endoplasmic Reticulum Stress
[MESH]
|Adrenomedullin/*genetics/*metabolism
[MESH]
|Animals
[MESH]
|Apoptosis
[MESH]
|Caspase 12/metabolism
[MESH]
|Cell Line
[MESH]
|Creatinine/blood
[MESH]
|Epithelial Cells
[MESH]
|Gene Expression
[MESH]
|Heat-Shock Proteins/metabolism
[MESH]
|Hydro-Lyases/blood
[MESH]
|Kidney Tubules/cytology
[MESH]
|Male
[MESH]
|Neuropeptides/*genetics/*metabolism
[MESH]
|Rats
[MESH]
|Rats, Sprague-Dawley
[MESH]
|Reperfusion Injury/blood/pathology/*prevention & control
[MESH]