SERPINB2 is a novel indicator of stem cell toxicity

Abstract

The toxicological evaluation of potential drug candidates is very important in the preclinical phase of drug development. Toxic materials may cause serious decline in stem cell function and loss of stemness. Indeed, we found that toxic exposure more profoundly suppressed the growth of stem cells than terminally differentiated fibroblasts. Importantly, toxic exposure suppressed stem cell migration and multi-lineage differentiation potential in vitro and in vivo. Moreover, early-response genes involved in stem cell properties such as self-renewal and differentiation capabilities can be used as specific markers to predict toxicity. In the present study, we also identified a labile toxic response gene, SERPINB2, which is significantly increased in response to various toxic agents in human stem cells in vitro and in vivo. Consistently, self-renewal, migration, and multi-lineage differentiation potential were markedly decreased following SERPINB2 overexpression. To the best of our knowledge, this is the first study to focus on the functions of SERPINB2 on the regenerative potential of stem cells in response to various existing chemicals, and the findings will facilitate the development of promising toxicity test platforms for newly developed chemicals.

SerpinB2 Regulates Immune Response in Kidney Injury and Aging

“…There are many mechanistic concepts about possible functions of SerpinB2, which are surprisingly heterogeneous and so far, have not resulted in a clear consensus. 11,17,19,21,31,32 In vitro, we found that SerpinB2 was highly upregulated in cultured PTECs after g-irradiation and after PMA treatment. In vivo, SerpinB2 was upregulated in tubular cells by a variety of stressors, such as aging, UUO, and IR.…”

SERPINB2 Is a Novel Indicator of Cancer Stem Cell Tumorigenicity in Multiple Cancer Types

“…In a previous study, we compared the gene expression profiles in TCDD-treated cells and non-treated cells to identify potential genes that were responsive to tumorigenic compound exposure using a large-scale gene expression analysis method: RNA sequencing. We observed a significant positive correlation between TCDD exposure and enhanced SERPINB2 expression among the analyzed genes [20]. The Gene Expression Omnibus (GEO) database was analyzed to verify the increased SERPINB2 expression with the initiation and progression of multiple cancer types.…”

An Endogenous Anti-aging Factor, Sonic Hedgehog, Suppresses Endometrial Stem Cell Aging through SERPINB2

“…In our previous study, we discovered a significant positive association between toxic exposure and increased SERPINB2 expression in local stem cells in vitro and in vivo. 32 We therefore hypothesized that both replicative and oxidative stress-induced senescence may enhance SERPINB2 expression, which in turn mediates the alleviating effect of SHH on senescence-induced endometrial stem cell dysfunctions. The gene datasets were filtered by the expression profiles of SERPINB2 in young patients (16) versus aged patients (17) or nonsenescent versus senescent cells.…”

“…30,31 In our previous study, we observed a positive correlation between toxic exposure and significantly enhanced SERPINB2 expression in adult stem cells in vitro and in vivo. 32 We therefore hypothesized in the present study that both replicative and oxidative stress-induced cellular senescence may enhance SERPINB2 expression and that it can regulate the effect of SHH on alleviating senescence-induced endometrial stem cell dysfunctions ( Figure 4A). Consistent with our hypothesis, replicative ( Figure 4B) and oxidative stress-induced ( Figure 4C) senescence significantly enhanced SERPINB2 expression at both the mRNA and protein levels.…”