Mesenchymal stem cells protect podocytes from apoptosis induced by high glucose via secretion of epithelial growth factor.
Mesenchymal stem cells protect podocytes from apoptosis induced by high glucose via secretion of epithelial growth factor.
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间充质干细胞通过分泌上皮生长因子保护足细胞免受高糖诱导的细胞凋亡
DOI：
10.1186/scrt314
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发表时间：
2013
影响因子：
7.5
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Li D;Wang N;Zhang L;Hanyu Z;Xueyuan B;Fu B;Shaoyuan C;Zhang W;Xuefeng S;Li R;Chen X
导读：足细胞凋亡及随后的损伤在糖尿病肾病（DN）中起致病作用。间充质干细胞（MSCs）是一种具有预防细胞凋亡和减少细胞损伤的治疗细胞。我们之前的研究发现MSCs可以保护肾脏免受糖尿病引起的损伤，但没有明显的植入。因此，我们评估了人脂肪源性间充质干细胞（hAd-MSCs）对高糖（HG）诱导的足细胞凋亡和损伤的影响及其潜在机制。方法采用流式细胞术、Western blot和共聚焦荧光显微镜观察HG在存在或不存在MSC-conditioned medium （CM）情况下24小时、48小时和72小时对足细胞凋亡和损伤的影响。采用基于抗体的细胞因子阵列鉴定介导因子，通过添加中和抗体（NtAb）阻断其功能或在培养基中添加重组细胞因子诱导其功能来验证。结果shad - msc - cm呈剂量依赖性地减少足细胞凋亡，降低足细胞cleaved caspase-3的表达，阻止足细胞synaptopodin和nephrin的表达减少并维持其正常排列。然而，人胚胎肺细胞(Wi38)-CM不能改善足细胞凋亡或损伤。共鉴定出12种浓度比为（MSC-CM/Wi38-CM） bbb10倍的细胞因子。上皮生长因子（EGF）因其已知的防止细胞凋亡的能力而被挑选出来。重组人EGF （rhEGF）对足细胞凋亡和损伤的抑制作用与hAd-MSC-CM相似，但在阻断EGF后，hAd-MSC-CM的有益作用显著下降。结论shad - mscs主要通过分泌可溶性EG抑制HG诱导的足细胞凋亡和损伤。
IntroductionThe apoptosis and subsequent injury of podocytes plays a pathogenic role in diabetic nephropathy (DN). Mesenchymal stem cells (MSCs) are promising therapeutic cells for preventing apoptosis and reducing cellular injury. Our previous study found that MSCs could protect kidneys from diabetes-induced injury without obvious engraftment. So we evaluated the effects of human adipose-derived MSCs (hAd-MSCs) on podocytic apoptosis and injury induced by high glucose (HG) and the underlying mechanisms.MethodsWe used flow cytometry, Western blot and confocal fluorescence microscopy to study podocytic apoptosis and injury induced by HG at 24 hours, 48 hours, and 72 hours in the presence or absence of MSC-conditioned medium (CM). An antibody-based cytokine array was used to identify the mediating factor, which was verified by adding the neutralizing antibody (NtAb) to block its function or adding the recombinant cytokine to the medium to induce its function.ResultshAd-MSC-CM reduced podocytic apoptosis in a dose-dependent manner, decreased the expression of podocytic cleaved caspase-3, and prevented the reduced expression and maintained the normal arrangement of podocytic synaptopodin and nephrin. However, human embryonic lung cell (Wi38)-CM failed to ameliorate podocytic apoptosis or injury. Twelve cytokines with concentration ratios (MSC-CM/Wi38-CM) >10-fold were identified. Epithelial growth factor (EGF) was singled out for its known ability to prevent apoptosis. Recombinant human EGF (rhEGF) prevented podocytic apoptosis and injury similarly to hAd-MSC-CM but, upon blockade of EGF, the beneficial effect of hAd-MSC-CM decreased dramatically.ConclusionshAd-MSCs prevent podocytic apoptosis and injury induced by HG, mainly through secreting soluble EG.
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影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1042/cbr20110004
发表时间：
2011-09-13
期刊：
Cell biology international reports
影响因子：
--
作者：
Coli A;Nocchi F;Lamanna R;Iorio M;Lapi S;Urciuoli P;Scatena F;Giannessi E;Stornelli MR;Passeri S
通讯作者：
Passeri S
影响因子：
7.5
作者：
Ben Azouna N;Jenhani F;Regaya Z;Berraeis L;Ben Othman T;Ducrocq E;Domenech J
通讯作者：
Domenech J
影响因子：
7.5
作者：
Chase LG;Lakshmipathy U;Solchaga LA;Rao MS;Vemuri MC
通讯作者：
Vemuri MC
DOI：
10.1152/ajpgi.00182.2007
发表时间：
2007-09-01
影响因子：
4.5
作者：
Sheng, George;Guo, Jun;Warner, Brad W.
通讯作者：
Warner, Brad W.