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
Affiliations
Jun He
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou 570208, Hainan Province, P.R. China
Jun Peng
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou 570208, Hainan Province, P.R. China
You Li
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou 570208, Hainan Province, P.R. China
Junwen Jiang
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou 570208, Hainan Province, P.R. China
Jiameng Li
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou 570208, Hainan Province, P.R. China
Long Lin
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou 570208, Hainan Province, P.R. China
Jian Wang
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou 570208, Hainan Province, P.R. China
Ying Xia
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou 570208, Hainan Province, P.R. China; Corresponding author
Summary: 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.
