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Role of endoplasmic reticulum stress in podocyte injury in diabetic nephropathy

Author: ZhangHong
Tutor: LiXueWang
School: Beijing Union Medical College
Course: Clinical
Keywords: Endoplasmic reticulum stress diabetic nephropathy podocyte apoptosis palmitate
CLC: R587.2
Type: PhD thesis
Year: 2010
Downloads: 32
Quote: 0
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BackgroundDiabetic nephropathy (DN) has become the second cause of end-stage renal disease (ESRD) in China. The pathogenesis of DN is complicated and thoroughly investigation is needed. Endoplasmic reticulum stress (ERS) is the reaction aimed to relieve the stress in the endoplasmic reticulum. However, constant ERS will lead to subsequent apoptosis. More data recently have revealed the important role of ERS in the pathogenesis of DN. However, further exploration of the accurate mechanism is still needed.ObjectiveTo investigate whether ERS is existed along podocyte damage in early stage of DN.MethodsC57BLKS db/db mice were studied at the age of6,9and12weeks. Each group was consisted of7db/db mouse and5db/m mouse as control. Mesangial matrix area percentage was analyzed in PASM stained slides. Wt-1was used as podocyte marker to evaluated podocyte density by number calculated in each glomerulus. Synaptopodin and glucose-regulated protein(GRP78) were stained simultaneously to analyze ERS in glomerulus. The apoptosis in renal tissure was detected by TUNEL. Confocal microscopy was applied to detect the GRP78change in podocytes stimulated by palmitate.Results(1) The mesangial matrix expanded in9week-old db/db mice and became more evident in some12week-old db/db mice compared with the control; GRP78expression became evident in db/db mice from6weeks, and the expression increased as to12weeks. At the same time, it was hardly detected in control groups. The disperse pattern of GRP78was consistent with that of podocytes. There was no significant apoptosis in renal tissues among every group examined, p>0.05.(2) GRP78was increased in podocytes stimulated by palmitate, and the cellular density was decreased.Conclusions(1) The mesangial matrix area expands and GRP78in podocytes is over expressed in early stage of mouse diabetic nephropathy. Both of them progresses with DN duration. No obvious apoptosis is observed in the renal tissues, suggesting ERS precedes apoptosis and might be effective as a protective factor.(2) Palmitate induces endoplasmic reticulum stress in podocytes.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetic coma and other complications
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