Lipocalin 2 decreases senescence of bone marrow-derived mesenchymal stem cells under sub-lethal doses of oxidative stress

Abstract

The regenerative potential of mesenchymal stem cells (MSCs) is impaired by cellular senescence, a multi factorial process that has various functions. However, pathways and molecules involved in senescence have not been fully identified. Lipocalin 2 (Lcn2) has been the subject of intensive research, due to its contribution to many physiological and pathophysiological conditions. The implication of Lcn2 has been reported in many conditions where senescence also occurs. In the present study, we evaluated the role of Lcn2 in the occurrence of senescence in human bone marrowderived mesenchymal stem cells (hB-MSCs) under oxidative conditions. When hB-MSCs were genetically engineered to over-express Lcn2 (MSC-Lcn2) and exposed to H 2 O 2 , the proliferation rate of the cells increased. However, the number of colonies and the number of cells that made up each colony in both MSC-V and MSC-Lcn2 cells decreased compared to those cultivated under normal conditions. Our results revealed that over-expression of recombinant Lcn2 in hB-MSCs decreases senescence induced by H 2 O 2 treatment. Senescent cells were observed in aged hB-MSCs; however, no alteration in the expression level of Lcn2 was detected compared to earlier passages. Finally, a higher amount of Lcn2 protein was detected in the plasma of the elderly than in young people.Our findings suggest that Lcn2 might restore the health and regeneration potential of MSCs by decreasing senescence.

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

“…Decreased senescence upon A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 9 hydrogen peroxide treatment was observed in the MCS-Lnc2 cell. These studies point to a role of NGAL in decreasing senescence under certain conditions [44].…”

Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential

“…The common overexpressed genes in promoting the survival of mesenchymal stem cells (MSCs) include v-Akt Murine Thymoma Viral Oncogene (AKT) [10], B-cell lymphoma 2 (Bcl-2) [11], heat shock protein 20 (Hsp20) [12], nuclear factor related (erythroid-derived 2)-like 2 (Nrf2) [13], heme oxygenase-1 (HO) [14,15], endothelial nitric oxide synthase (eNOS) [16], connexin 43 (Cx43) [17], and hypoxia inducible factor-1α (HIF-1α) [18]. Other overexpressed genes, such as wild-type p53 inducible phosphatase-1 (WIP-1) [19] and lipocalin 2 (Lcn2) [20], could decrease MSC senescence during the process. However, genetic manipulation of MSCs has limited clinical benefit due to its inherent risks during genetic modification, such as random integration into the host genome inducing mutations [21].…”

Lipocalin‐2 enhances angiogenesis in rat brain endothelial cells via reactive oxygen species and iron‐dependent mechanisms

“…Over‐expression of LCN2‐enhanced cell proliferation and decreased senescence induced by H 2 O 2 treatment in bone‐marrow‐derived mesenchymal stem cells, suggesting that LCN2 might be protective against oxidative stress (Bahmani et al . ). Alternatively, LCN2‐induced elevations in iron may increase ROS via Fenton‐like reactions.…”