Neural stem cells secrete factors that promote auditory cell proliferation via a leukemia inhibitory factor signaling pathway.
The capacity for perpetual self-renewal is one of the main characteristics of stem cells. Little is known about the effect of embryonic neural stem cell (NSC)-secreted factors on auditory cell proliferation in vitro. In the present work, two auditory cell types were cultured in the presence of NSC-secreted molecules and were evaluated in vitro. Our results demonstrated that both cell viability and cell proliferation were significantly enhanced upon treatment with NSC conditioned medium, which contains significantly elevated levels of leukemia inhibitory factor (LIF) secreted by NSCs. The NSC conditioned medium not only activated the expression of leukemia inhibitory factor receptor in House Ear Institute-organ of Corti 1 cells but also up-regulated the LIF downstream signal transducers and activators of transcription (STAT) 1 and STAT3. Blocking either the LIF signaling pathway with neutralizing antibodies or the downstream Janus kinase (JAK)/STAT pathway with JAK2 inhibitor AG490 resulted in a dose-dependent inhibition of cell proliferation, suggesting that NSC-secreted molecules promote auditory cell survival via the regulatory LIF/JAK/STAT signaling pathway.
Chen
Hsin-Chien
HC
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Ma
Hsin-I
HI
Sytwu
Huey-Kang
HK
Wang
Hsing-Won
HW
Chen
Chia-Chi V
CC
Liu
Shu-Chen
SC
Chen
Chi-Huang
CH
Chen
Hang-Kang
HK
Wang
Chih-Hung
CH
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D017077:Culture Media, Conditioned / Q000494:pharmacology; D007150:Immunohistochemistry; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
D017077:Culture Media, Conditioned; D053605:Leukemia Inhibitory Factor