Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction.
Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction.
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DOI：
10.1186/s13287-015-0012-6
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发表时间：
2015-03-11
影响因子：
7.5
通讯作者：
Park HC
中科院分区：
文献类型：
--
作者：
Choi HY;Lee HG;Kim BS;Ahn SH;Jung A;Lee M;Lee JE;Kim HJ;Ha SK;Park HC
来自肾源性间充质干细胞（KMSCs）的微颗粒（MPs）最近被报道通过传递促血管生成效应器改善缺血肾脏的小管周围毛细血管（PTC）的稀缺性。本研究旨在探讨kmsc来源的MPs是否通过在体外改善人脐静脉内皮细胞（HUVEC）的内皮到间充质转化（EndoMT）和在体内保留单侧输尿管梗阻（UUO）肾脏的PTC来显示抗纤维化作用。从KMSC上清中分离的MPs与HUVEC共培养，以评估其对内皮细胞的体外生物学效应。小鼠UUO损伤后经尾静脉注射MPs，观察其抗纤维化和节省PTC的作用。马氏三色、F4/80、α-平滑肌肌动蛋白（α-SMA）染色检测肾小管间质损伤及炎症细胞浸润，CD31染色检测PTC稀化指数。kmsc来源的MPs显著改善了内皮细胞内皮细胞（EndoMT），促进了TGF-β1处理的HUVEC体外增殖。体内给药kmsc来源的MPs可显著抑制PTC内皮细胞的EndoMT，并改善UUO肾脏中PTC的稀离性。此外，kmsc来源的MPs抑制UUO小鼠的炎症细胞浸润和小管间质纤维化，分别通过降低F4/80和α- sma阳性细胞和马松三色染色来证明。我们的研究结果表明，kmsc来源的MPs通过抑制EndoMT改善PTC的稀散性，并通过抑制小管间质纤维化来防止肾损害的进展。
Microparticles (MPs) derived from kidney-derived mesenchymal stem cells (KMSCs) have recently been reported to ameliorate rarefaction of peritubular capillaries (PTC) in ischemic kidneys via delivery of proangiogenic effectors. This study aimed to investigate whether KMSC-derived MPs show anti-fibrotic effects by ameliorating endothelial-to-mesenchymal transition (EndoMT) in human umbilical vein endothelial cells (HUVEC) in vitro and by preserving PTC in kidneys with unilateral ureteral obstruction (UUO) in vivo. MPs isolated from the supernatants of KMSC were co-cultured with HUVEC to assess their in vitro biologic effects on endothelial cells. Mice were treated with MPs via the tail vein after UUO injury to assess their anti-fibrotic and PTC sparing effects. Renal tubulointerstitial damage and inflammatory cell infiltration were examined with Masson’s trichrome, F4/80 and α-smooth muscle actin (α-SMA) staining and PTC rarefaction index was determined by CD31 staining. KMSC-derived MPs significantly ameliorated EndoMT and improved in vitro proliferation of TGF-β1 treated HUVEC. In vivo administration of KMSC-derived MPs significantly inhibited EndoMT of PTC endothelial cells and improved PTC rarefaction in UUO kidneys. Furthermore, administration of KMSC-derived MPs inhibited inflammatory cell infiltration as well as tubulointerstitial fibrosis in UUO mice as demonstrated by decreased F4/80 and α-SMA-positive cells and Masson’s trichrome staining, respectively. Our results suggest that KMSC-derived MPs ameliorate PTC rarefaction via inhibition of EndoMT and protect against progression of renal damage by inhibiting tubulointerstitial fibrosis.
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影响因子：
19.6
作者：
Chen, Jun;Park, Hyeong-Cheon;Addabbo, Francesco;Ni, Jie;Pelger, Edward;Li, Houwei;Plotkin, Matthew;Goligorsky, Michael S.
通讯作者：
Goligorsky, Michael S.
影响因子：
3.7
作者：
Choi HY;Moon SJ;Ratliff BB;Ahn SH;Jung A;Lee M;Lee S;Lim BJ;Kim BS;Plotkin MD;Ha SK;Park HC
通讯作者：
Park HC
影响因子：
82.9
作者：
Zeisberg, Elisabeth M.;Tarnavski, Oleg;Kalluri, Raghu
通讯作者：
Kalluri, Raghu
影响因子：
6.1
作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
DOI：
10.1097/01.asn.0000018408.51388.57
发表时间：
2002-07-01
影响因子：
13.6
作者：
Ohashi, R;Shimizu, A;Yamanaka, N
通讯作者：
Yamanaka, N