Attenuation of diabetic nephropathy in diabetes rats induced by streptozotocin by regulating the endoplasmic reticulum stress inflammatory response.
The endoplasmic reticulum (ER) is capable of sensing metabolic and stress parameters and integrating intra- and extracellular signals to support a coordinated cell response. In the present study, we verified the hypothesis that 4-phenylbutyric acid (4-PBA), a chemical chaperone, prevented the progression of diabetic nephropathy (DN). Male Sprague-Dawley rats were randomly divided into 3 groups: a normal control group, a DN group, and a DN model plus 4-PBA treatment group (PBA). The DN model was induced by injection of streptozotocin with uninephrectomy. The dosage of 4-PBA treatment was gavaged at a dose of 1 g/kg body weight each day for 12 weeks. The expression of the ER stress indicators significantly increased in the kidney of DN rats within the indicated period. Moreover, the expression of phosphorylated c-JUN NH(2)-terminal kinase, the monocyte chemoattractant protein-1, and the final fibrotic effector all elevated markedly in the kidney of DN rats. Urinary protein excretion rate and the concentration of urinary monocyte chemoattractant protein-1 were higher than those in the normal control group. Treatment with 4-PBA can suppress the expression of the glucose-regulated protein 78 and the phosphorylation of the PKR-like ER kinase, both of which are ER stress indicators; renoinflammatory signal; and the expression of inflammatory cytokines and fibrosis factors. It also can inhibit the increase in urinary protein excretion rate and urinary monocyte chemoattractant protein-1. In conclusion, 4-PBA exerts a marked renoprotective effect possibly due to modulating ER stress and related inflammatory cascade.
Qi
Wei
W
Department of Nephrology, Xinqiao Hospital, The Third Military Medical University, Chongqing, People's Republic of China,
Mu
Jiao
J
Luo
Zhi-Feng
ZF
Zeng
Wei
W
Guo
Yan-Hong
YH
Pang
Qi
Q
Ye
Zi-Lin
ZL
Liu
Li
L
Yuan
Fa-Huan
FH
Feng
Bing
B
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism / Q000652:urine; D016207:Cytokines / Q000378:metabolism / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D010654:Phenylbutyrates / Q000627:therapeutic use*; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D010654:Phenylbutyrates; C075773:4-phenylbutyric acid; D048031:JNK Mitogen-Activated Protein Kinases