Anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys.
Anti-inflammatory drugs suppress ultrasound-mediated mesenchymal stromal cell tropism to kidneys.
复制标题
DOI：
10.1038/s41598-017-08887-x
复制
发表时间：
2017-08-17
影响因子：
4.6
通讯作者：
Frank JA
中科院分区：
文献类型：
--
作者：
Burks SR;Nguyen BA;Bresler MN;Nagle ME;Kim SJ;Frank JA
Mesenchymal stromal cells (MSC) are potential renal therapeutics. Clinically, results are mixed partly because MSC tropism to kidneys is minimal following infusion. Ultrasound augmentation of the renal microenvironment is becoming increasingly-important in renal MSC therapies. We demonstrated pulsed-focused-ultrasound (pFUS) increases enhanced homing permeability and retention of MSC in mouse kidneys. Here, we characterized the temporal proteomic response to pFUS in mouse kidneys and its association with MSC tropism. pFUS induced molecular cascades of initial increases in tumor necrosis factor-α (TNFα) and interleukin (IL)-1α, that activated nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and cyclooxygenase-2 (COX2) pathways without cell death. This was followed by a 24–48 hour-long response of increased cell adhesion molecules (CAM), trophic and anti-inflammatory factors. Pretreating animals with anti-inflammatory drugs etanercept (TNFα inhibitor), anakinra (IL-1 receptor antagonist), prednisone (NFκB translocation inhibitor), or ibuprofen (COX inhibitor) suppressed molecular changes and inhibited renal MSC tropism. We further examined the role of COX2 using a COX2-knock-out mouse where pFUS was unable to increase MSC tropism. These results demonstrate that renal micro-environmental changes induce MSC tropism and could influence the therapeutic efficacy of MSC. Optimizing the microenvironment and understanding drug effects will enable improvements in MSC therapies for renal disease.
登录
查看更多内容
影响因子：
6.3
作者：
Raymond, Scott B.;Skoch, Jesse;Bacskai, Brian J.
通讯作者：
Bacskai, Brian J.
影响因子：
5.5
作者：
Deplano, Simona;Cook, H. Terence;Behmoaras, Jacques
通讯作者：
Behmoaras, Jacques
影响因子：
2.5
作者：
Stagg, J.;Galipeau, J.
通讯作者：
Galipeau, J.
影响因子：
5.2
作者：
Ziadloo, Ali;Burks, Scott R.;Gold, Eric M.;Lewis, Bobbi K.;Chaudhry, Aneeka;Merino, Maria J.;Frenkel, Victor;Frank, Joseph A.
通讯作者：
Frank, Joseph A.
影响因子：
5.2
作者：
Tebebi, Pamela A.;Burks, Scott R.;Kim, Saejeong J.;Williams, Rashida A.;Nguyen, Ben A.;Venkatesh, Priyanka;Frenkel, Victor;Frank, Joseph A.
通讯作者：
Frank, Joseph A.