KLF2 Regulates Neural Differentiation of Dental Pulp-derived Stem Cells by Modulating Autophagy and Mitophagy

Abstract

Transplantation of stem cells for treating neurodegenerative disorders is a promising future therapeutic approach. However, the molecular mechanism underlying the neuronal differentiation of mesenchymal stem cells remains inadequately explored. Therefore, the current study aims to de ne the regulatory role of KLF2 (Kruppel-like factor 2) during the neural differentiation (ND) of dental pulp-derived stem cells (DPSC). Herein, we showed that the expression level of KLF2, autophagy and mitophagy-associated markers were signi cantly elevated during ND of DPSC. We next validated our results using the chemicalmediated loss-and gain-of-function approaches. We found that the KLF2 inhibitor, GGPP (geranylgeranyl pyrophosphate) signi cantly reduces the ND of DPSC. Inversely, KLF2 overexpression was accomplished by using the KLF2 inducer, GGTI-298 (geranylgeranyl transferase inhibitor-298) which accelerated the molecular phenomenon of DPSC's commitment towards ND, indicating the crucial function of KLF2 in neurogenesis. Moreover, we found that the KLF2 positively regulated autophagy, mitophagy, and the Wnt5a signaling pathway during neurogenesis. Furthermore, we measured the oxygen consumption rate (OCR), and the extracellular acidi cation rate (ECAR) during ND in the presence of a KLF2 inducer or KLF2 inhibitor using the Xe ux analyzer. We found that most of the ECAR and OCR parameters were signi cantly increased during ND and inhibition of KLF2 marginally reversed them towards DPSC's cellular bioenergetics. However, KLF2 overexpression shifted the cellular energy metabolism towards quiescent. Cumulatively, our ndings provide the rst evidence that the KLF2 critically regulates the neurogenesis of DPSC by inducing autophagy and mitophagy.

miRNA‑21 promotes the progression of acute liver failure via the KLF6/autophagy/IL‑23 signaling pathway

“…KLF4 strengthens the sensitivity of colon cancer cells to 5-fluorouracil by targeting RAB26 to restrain autophagy ( 36 ). KLF2 critically regulates the neurogenesis of dental pulp-derived stem cells by inducing mitophagy and autophagy ( 37 ). The present study demonstrated that KLF6 promoted autophagy, and KLF6 blocks miR-21-induced increases in IL-23 expression.…”