Adipose tissue-derived stem cells secrete CXCL5 cytokine with neurotrophic effects on cavernous nerve regeneration.
Adipose tissue-derived stem cells secrete CXCL5 cytokine with neurotrophic effects on cavernous nerve regeneration.
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DOI：
10.1111/j.1743-6109.2010.02128.x
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Lin CS
中科院分区：
文献类型：
--
作者：
Zhang H;Yang R;Wang Z;Lin G;Lue TF;Lin CS
以前我们报道过旁分泌作用可能介导了脂肪组织来源的干细胞（ADSC）对大鼠海绵体神经（CN）损伤模型的治疗作用。从ADSC分泌物中筛选出潜在的神经营养因子，并对其中最有潜力的一种进行检测，明确其神经营养作用的分子机制。用ADSC和阴茎平滑肌细胞（PSMC）的条件培养液培养大鼠盆大神经节（MPG）。用细胞因子抗体阵列探测这两种培养基中的细胞因子表达。通过酶联免疫吸附测定（ELISA）定量这两种培养基中的CXCL 5细胞因子。通过蛋白质印迹法在神经母细胞瘤细胞系BE（2）C和SH-SY 5 Y以及雪旺细胞系RT 4-D 6P 2 T中测试CXCL 5对JAK/STAT的激活。CXCL 5和JAK/STAT参与ADSC条件培养基的神经营养作用分别用抗CXCL 5抗体和JAK抑制剂AG 490证实。通过测量MPG培养物中的神经突长度来量化ADSC和PSMC条件培养基的神经营养作用。通过ELISA定量这两种培养基中CXCL 5的分泌。JAK/STAT通过CXCL 5的活化通过蛋白质印迹上的STAT 1和STAT 3磷酸化的光密度测定法定量。MPG神经突长度在ADSC中比在PSMC条件培养基中显着更长。CXCL 5在ADSC中的分泌比在PSMC条件培养基中高8倍。抗CXCL 5抗体阻断ADSC条件培养基的神经营养作用。在RT 4-D 6P 2 T雪旺细胞中，0至50 ng/ml的CXCL 5浓度依赖性地激活JAK/STAT。在50 ng/ml时，CXCL 5激活JAK/STAT的时间依赖性，在45 min达到峰值。AG 490阻断这些活动以及ADSC条件培养基的神经营养作用。CXCL 5在ADSC中高水平分泌，促进MPG轴突生长，并激活雪旺细胞中的JAK/STAT。CXCL 5可能有助于ADSC对CN损伤诱导的ED的治疗效果。
Previously we reported that paracrine actions likely mediated the therapeutic effects of adipose tissue-derived stem cells (ADSC) on a rat model of cavernous nerve (CN) injury. To identify potential neurotrophic factors in ADSC’s secretion, test the most promising one, and identify the molecular mechanism of its neurotrophic action. Rat major pelvic ganglia (MPG) were cultured in conditioned media of ADSC and penile smooth muscle cells (PSMC). Cytokine expression in these two media was probed with a cytokine antibody array. CXCL5 cytokine was quantified in these two media by enzyme-linked immunosorbent assay (ELISA). Activation of JAK/STAT by CXCL5 was tested in neuroblastoma cell lines BE(2)C and SH-SY5Y as well as in Schwann cell line RT4-D6P2T by western blot. Involvement of CXCL5 and JAK/STAT in ADSC-conditioned medium’s neurotrophic effects was confirmed with anti-CXCL5 antibody and JAK inhibitor AG490, respectively. Neurotrophic effects of ADSC and PSMC-conditioned media were quantified by measuring neurite length in MPG cultures. Secretion of CXCL5 in these two media was quantified by ELISA. Activation of JAK/STAT by CXCL5 was quantified by densitometry on western blots for STAT1 and STAT3 phosphorylation. MPG neurite length was significantly longer in ADSC than in PSMC-conditioned medium. CXCL5 was secreted 8 times higher in ADSC than in PSMC-conditioned medium. Anti-CXCL5 antibody blocked the neurotrophic effects of ADSC-conditioned medium. CXCL5 activated JAK/STAT concentration-dependently from 0 to 50 ng/ml in RT4-D6P2T Schwann cells. At 50 ng/ml, CXCL5 activated JAK/STAT time-dependently, peaking at 45 min. AG490 blocked these activities as well as the neurotrophic effects of ADSC-conditioned medium. CXCL5 was secreted by ADSC at a high level, promoted MPG neurite growth, and activated JAK/STAT in Schwann cells. CXCL5 may contribute to ADSC’s therapeutic efficacy on CN injury-induced ED.
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DOI：
10.1111/j.1743-6109.2009.01697.x
发表时间：
2010-04
期刊：
The journal of sexual medicine
影响因子：
--
作者：
Huang YC;Ning H;Shindel AW;Fandel TM;Lin G;Harraz AM;Lue TF;Lin CS
通讯作者：
Lin CS
DOI：
10.1111/j.1743-6109.2008.01190.x
发表时间：
2009-03
期刊：
The journal of sexual medicine
影响因子：
--
作者：
Lin G;Banie L;Ning H;Bella AJ;Lin CS;Lue TF
通讯作者：
Lue TF
DOI：
10.1111/j.1743-6109.2008.01194.x
发表时间：
2009-03
期刊：
The journal of sexual medicine
影响因子：
--
作者：
Bella AJ;Lin G;Lin CS;Hickling DR;Morash C;Lue TF
通讯作者：
Lue TF
影响因子：
3.5
作者：
Lin, Guiting;Bella, Anthony J.;Lin, Ching-Shwun
通讯作者：
Lin, Ching-Shwun
影响因子：
23.4
作者：
Fall, Papa Ahmed;Izikki, Mohamed;Yiou, Rene
通讯作者：
Yiou, Rene