CD44 mediates stem cell mobilization to damaged lung via its novel transcriptional targets, Cortactin and Survivin
المؤلف | Ouhtit, Allal |
المؤلف | Thouta, Rajesh |
المؤلف | Zayed, Hatem |
المؤلف | Gaur, Rajiv L |
المؤلف | Fernando, Augusta |
المؤلف | Rahman, Mizanur |
المؤلف | Welsh, David A |
تاريخ الإتاحة | 2020-07-20T05:59:48Z |
تاريخ النشر | 2020-05-01 |
اسم المنشور | International Journal of Medical Sciences |
المعرّف | http://dx.doi.org/10.7150/ijms.33125 |
الاقتباس | Ouhtit A, Thouta R, Zayed H, Gaur RL, Fernando A, Rahman M, Welsh DA. CD44 mediates stem cell mobilization to damaged lung via its novel transcriptional targets, Cortactin and Survivin. Int J Med Sci 2020; 17(1):103-111. doi:10.7150/ijms.33125. Available from http://www.medsci.org/v17p0103.htm |
الملخص | Beyond their role in bone and lung homeostasis, mesenchymal stem cells (MSCs) are becoming popular in cell therapy. Various insults may disrupt the repair mechanisms involving MSCs. One such insult is smoking, which is a major risk factor for osteoporosis and respiratory diseases. Upon cigarette smoke-induced damage, a series of reparatory mechanisms ensue; one such mechanism involves Glycosaminoglycans (GAG). One of these GAGs, namely hyaluronic acid (HA), serves as a potential therapeutic target in lung injury. However, much of its mechanisms of action through its major receptor CD44 remains unexplored. Our previous studies have identified and functionally validated that both cortactin (CTTN: marker of motility) and Survivin (BIRC5: required for cell survival) act as novel HA/CD44-downstream transcriptional targets underpinning cell motility. Here, human MSCs were treated with "" smoke to investigate the effects of cigarette smoke condensate (CSC) on these HA-CD44 novel signaling pathways. Our results show that CSC decreased the expression of both CD44 and its downstream targets CTTN and BIRC5 in MSCs, and that HA reversed these effects. Interestingly, CSC inhibited migration and invasion of MSCs upon CD44-targeted RNAi treatment. This shows the importance of CD44-HA/CTTN and CD44-HA/BIRC5 signaling pathways in MSC motility, and further suggests that these signaling pathways may provide a novel mechanism implicated in migration of MSCs during repair of lung tissue injury. These findings suggest that one should use caution before utilizing MSC from donors with history of smoking, and further pave the way towards the development of targeted therapeutic approaches against CD44-associated diseases. |
اللغة | en |
الناشر | Ivyspring International Publisher |
الموضوع | CD44 Cortactin Survivin cigarette smoke mesenchymal stem cells |
النوع | Article |
الصفحات | 103-111 |
رقم العدد | 1 |
رقم المجلد | 17 |
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