|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Suppression of the PI3K–Akt pathway is involved in the decreased adhesion and migration of bone marrow-derived mesenchymal stem cells from non-obese diabetic mice
Liren Li*1, Yunfei Xia*1, Zhiwei Wang*, Xiaolei Cao†, Zhanyun Da*, Gengkai Guo*, Jie Qian*, Xia Liu*, Yaping Fan*, Lingyun Sun‡, Aiming Sang*2 and Zhifeng Gu*
*Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, Peoples Republic of China, †Department of Pathology, Medical College of Nantong University, Nantong, Jiangsu 226001, Peoples Republic of China, and ‡Department of Rheumatology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 21008, Peoples Republic of China
T1DM (type 1 diabetes mellitus) is an autoimmune disease characterized by T-cell-mediated damage of islet β-cells. The pathology of NOD (non-obese diabetic) mouse involves the insulitis induced by infiltration of T-cells, a similar pathogenic mechanism in T1DM patient. BM-MSCs (bone marrow mesenchymal stem cells) are multipotent progenitor cells that can be isolated from a number of sources. Recent studies have shown that transplantation of MSCs to the NOD mice could prevent the process and have the therapeutic effects on T1DM. In our studies, we have found that migration and adhesion of BM-MSCs from NOD mice were suppressed compared with the BM-MSCs from ICR (imprinting control region) mice, accompanying with the abnormal distribution of FAK (focal adhesion kinase) and F-actin (filamentous actin). Further, we have found that the activation of PI3K (phosphoinositide 3-kinase)–Akt pathway was suppressed in BM-MSCs from NOD mice. When the PI3K–Akt pathway was inhibited by LY294002, the adhesion and migration of BM-MSCs from ICR mice were suppressed as well. These results indicated that the suppression of PI3K–Akt pathway is involved in the decreased adhesion and migration of BM-MSCs from NOD mice.
Key words: adhesion, bone marrow, mesenchymal stem cell, migration, non-obese diabetic mice, type 1 diabetes mellitus
Abbreviations: BM-MSCs, bone marrow mesenchymal stem cells, DMEM, Dulbecco's modified Eagle's medium, F-actin, filamentous actin, FAK, focal adhesion kinase, ICR, imprinting control region, LN, laminin, NOD, non-obese diabetic, PI3K, phosphoinositide 3-kinase, T1DM, type 1 diabetes mellitus
1Liren Li and Yunfei Xia contributed equally to this work.
2To whom correspondence should be addressed (email firstname.lastname@example.org).
Received 28 July 2010/7 March 2011; accepted 30 March 2011
Published as Cell Biology International Immediate Publication 30 March 2011, doi:10.1042/CBI20100544
© The Author(s) Journal compilation © 2011 Portland Press Limited