Premium
Endoplasmic reticulum stress and diabetic nephropathy
Author(s) -
Shevalye Hanna,
Watcho Pierre,
Lupachyk Sergey,
Obrosova Irina G
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.686.16
Subject(s) - unfolded protein response , medicine , endocrinology , endoplasmic reticulum , albuminuria , diabetic nephropathy , diabetes mellitus , tauroursodeoxycholic acid , chemistry , biochemistry
These experiments evaluated the role for endoplasmic reticulum (ER) stress in prediabetic (PDN) and diabetic (DN) nephropathies. In study 1, control and STZ‐diabetic rats were treated with or without the chemical chaperone trimethylamine‐N‐oxide (TMAO), 110 mg kg −1 d −1 , for 12 wks. In study 2, C57Bl6/J mice were fed normal or high‐fat (HFD) diets for 16 wks, and then maintained with or without treatment with salubrinal, a selective inhibitor of eIF2alpha dephosphorylation. In study 1, diabetes‐induced renal ER stress was manifested by increased phospho‐PERK, total PERK, and phospho‐PERK/total PERK ratio and by decreased phospho‐eIF2alpha and phospho‐eIF2alpha/total eIF2alpha ratio. CHOP increased by 18%, but the difference with controls was not significant (p=0.073), and BiP remained unchanged. TMAO reduced diabetes‐associated albuminuria, mesangial expansion, fibronectin accumulation, and collagen deposition, without affecting podocyte loss. In the HFD study, salubrinal blunted renal cortex collagen deposition, indicative of the importance of ER stress in PDN. Salubrinal improved HFD‐induced glucose intolerance, without alleviating albuminuria. These findings implicate ER stress in the development of PDN and DN and identify a new therapeutic target.