Journal of Regenerative Medicine & Tissue Engineering

Journal of Regenerative Medicine & Tissue Engineering

ISSN 2050-1218
Original Research

Modulation of mTOR and autophagy in hibernating hamster lung and the application of the potential mechanism to improve the recellularization process of decellularized lung scaffolds

Fate Talaei

Correspondence: Fate Talaei Talaei@irimc.org

Author Affiliations

Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14171, Iran.

Abstract

During hibernation, hamsters cycle through periods of deep cooling (torpor) and re-warming (arousal). Reversible lung remodeling was previously observed through hibernation, where smooth muscle actin (SMA) expression was increased during torpor and normalized at arousal, sustaining lung structure throughout torpor. In the present research, the activation of mTOR (mammalian target of rapamycin) which is known to have an important role in remodeling and SMA protein expression was studied in hamster lung. Further, lung serotonin level known to modulate mTOR pathway was investigated. To determine if an increase of serotonin in lung tissue could be affecting SMA expression, cell number and cell matrix adhesion molecules, the effect of serotonin on Human Bronchial Smooth Muscle Cells (HBSMC) was investigated. Further, the potential application of serotonin in recellularization of decellularized rat lungs was studied in vitro. In hibernating hamster, mTOR, p-Akt and p-S6 levels decreased during torpor phase but were all upregulated during early arousal. Autophagy increased during torpor and reached maximum value during arousal. Serotonin treatment of HBSMC increased cell number and protein synthesis including SMA expression. It activated mTOR while increasing the expression of adhesion molecules, integrin α1, β1 and β-sarcoglycan in cells. Further, serotonin increased cell attachment to decellularized lung matrix, supporting ECM structure. Aberrations in proteostasis have negative effects on cellular growth and metabolism. This research provides new information on regulation of proteostasis in hibernating hamster lung with potential implications on regenerative medicine. It accordingly, further introduces a new approach to more efficient recellularization of lung scaffolds ex vivo.

Keywords: Serotonin, adhesion molecules, smooth muscle actin, reactive oxygen species

ISSN 2050-1218
Volume 3
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