scholarly journals Kallikrein Gene Transfer Protects Against Ischemic Stroke by Promoting Glial Cell Migration and Inhibiting Apoptosis

Hypertension ◽  
2004 ◽  
Vol 43 (2) ◽  
pp. 452-459 ◽  
Author(s):  
Chun-Fang Xia ◽  
Hang Yin ◽  
Cesar V. Borlongan ◽  
Lee Chao ◽  
Julie Chao
Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Susumu Yamaguchi ◽  
Nobutaka Horie ◽  
Katsuya Satoh ◽  
Yoichi Morofuji ◽  
Tsuyoshi Izumo ◽  
...  

Background and purpose: Cell transplantation therapy holds great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is uncertain. We investigate regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischemic stroke. Methods: The value of platelet-derived growth factor (PDGF)-BB secreted from human mesenchymal stem cells (hMSC) was analyzed regarding in two age groups; young (20-30 years) and old (57-65 years) in vitro. Male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion, and received young or old hMSC trans-arterially at 24 h after stroke. Functional recovery was assessed with modified neurological severity score (mNSS). Structural recovery was assessed on neovascularization and endogenous cell migration as well as trophic factor secretion. Results: The value of PDGF-BB was significantly higher in young hMSC (40.47±4.29 pg/ml/10 4 cells) than that in old hMSC (25.35±3.16 pg/ml/10 4 cells; P =0.02) and negatively correlated with age ( P =0.048, r=-0.79, Spearman). Rats treated with young hMSC (3.7±0.6) showed better behavior recovery in mNSS with prevention of brain atrophy than that with control (6.1±0.5) or old (5.2±0.7) at D21 ( P <0.01). The number of RECA-1 and PDGFR-β double positive vessels in rat with young hMSC (113±48.6/mm 2 ) was higher than that in control (61.5±35.9/mm 2 ) or old (76.9±36.9/mm 2 ) suggesting vessel maturation ( P <0.01). Interestingly, migration of neural stem/progenitor cells expressing Musashi-1 positively correlated with astrocyte process alignment ( P <0.01, r=0.27; Spearman), which was more pronounced in young hMSC ( P <0.05). Conclusions: Aging of hMSC may be the critical factor which affects outcome of cell therapy, and transplantation of young hMSC could provide better functional recovery by vessel maturation and endogenous cell migration potentially due to dominance of trophic factor secretion.


2016 ◽  
Vol 139 (3) ◽  
pp. 497-509 ◽  
Author(s):  
Christopher Katnik ◽  
Angela Garcia ◽  
Adam A. Behensky ◽  
Ilya E. Yasny ◽  
Alex M. Shuster ◽  
...  

2013 ◽  
Vol 453 (2) ◽  
pp. 201-208 ◽  
Author(s):  
Chang-Chun Wang ◽  
Hsiao-Fan Lo ◽  
Shu-Yu Lin ◽  
Hungwen Chen

GCM1 (glial cell missing 1) is a short-lived transcription factor essential for placental development. The F-box protein, FBW2 (F-box and WD-repeat domain-containing 2), which contains five WD (tryptophan–aspartate) repeats, recognizes GCM1 and mediates its ubiquitination via the SCFFBW2 E3 ligase complex. Although the interaction between GCM1 and FBW2 is facilitated by GCM1 phosphorylation, it is possible that this interaction might be regulated by additional cellular factors. In the present study, we perform tandem-affinity purification coupled with MS analysis identifying RACK1 (receptor for activated C-kinase 1) as an FBW2-interacting protein. RACK1 is a multifaceted scaffold protein containing seven WD repeats. We demonstrate that the WD repeats in both RACK1 and FBW2 are required for the interaction of RACK1 and FBW2. Furthermore, RACK1 competes with GCM1 for FBW2 and thereby prevents GCM1 ubiquitination, which is also supported by the observation that GCM1 is destabilized in RACK1-knockdown BeWo placental cells. Importantly, RACK1 knockdown leads to decreased expression of the GCM1 target gene HTRA4 (high-temperature requirement protein A4), which encodes a serine protease crucial for cell migration and invasion. As a result, migration and invasion activities are down-regulated in RACK1-knockdown BeWo cells. The present study reveals a novel function for RACK1 to regulate GCM1 activity and placental cell migration and invasion.


Author(s):  
Patrick Cafferty ◽  
Xiaojun Xie ◽  
Kristen Browne ◽  
Vanessa J. Auld

1999 ◽  
Vol 82 (2) ◽  
pp. 156-162 ◽  
Author(s):  
Harold A. Fernandez ◽  
Klaus Kallenbach ◽  
Graziano Seghezzi ◽  
Eugene Grossi ◽  
Stephen Colvin ◽  
...  

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