SENP1 facilitates OM-MSC differentiation through activating OPTN-mediated mitophagy to mitigate the neurologic impairment following ICH

Jun He; Jun Peng; You Li; Junwen Jiang; Jiameng Li; Long Lin; Jian Wang; Ying Xia

doi:10.1016/j.isci.2024.109865

SENP1 facilitates OM-MSC differentiation through activating OPTN-mediated mitophagy to mitigate the neurologic impairment following ICH

iScience. 2024 Apr 30;27(6):109865. doi: 10.1016/j.isci.2024.109865. eCollection 2024 Jun 21.

Authors

Jun He¹, Jun Peng¹, You Li¹, Junwen Jiang¹, Jiameng Li¹, Long Lin¹, Jian Wang¹, Ying Xia¹

Affiliation

¹ Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou 570208, Hainan Province, P.R. China.

Abstract

Previous studies have indicated the neuroprotective effect of olfactory mucosa mesenchymal stem cells (OM-MSCs) on brain injury. Intracerebral hemorrhage (ICH) models were established in rats by injecting autologous blood. SENP1 expression was enhanced in neurons but decreased in astrocytes compared to that in OM-MSCs. Overexpression of SENP1 promoted the proliferation and neuronal differentiation, while inhibiting the astrocytic differentiation of OM-MSCs. Conversely, its knockdown had the opposite effect. Moreover, OM-MSCs reduced neurological dysfunction in rats after ICH, and the neuroprotective effect of OM-MSCs could be further enhanced by SENP1 overexpression. In addition, SENP1 promoted mitophagy, which might be related to SENP1-mediated OPTN deSUMOylation. Furthermore, SENP1 promoted neuronal differentiation of OM-MSCs through mitophagy mediated by OPTN. Similar to SENP1, OPTN transfection further enhanced the remission effect of OM-MSC on ICH rats. SENP1 promoted neuronal differentiation of OM-MSCs through OPTN-mediated mitophagy to improve neurological deficits in ICH rats.

Keywords: Biological sciences; Cell biology; Molecular biology; Stem cells research.