Translin modulates mesenchymal cell proliferation and differentiation in mice

Ikeuchi, Yukiko; Imanishi, Azusa; Sudo, Katsuko; Fukunaga, Takako; Yokoi, Aya; Matsubara, Leo; Goto, Chie; Fukuoka, Tetsuo; Kuronuma, Kana; Kono, Ruri; Hasegawa, Natsumi; Asano, Shigetaka; Ito, Mitsuhiro

doi:10.1016/j.bbrc.2018.08.141

Cited by 7 publications

(13 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although our present study has identified several factors that may account for preserving glucose tolerance in translin KO mice, the molecular mechanism underlying their robust adiposity remains unclear. Recent studies show that translin KO mice have altered mesenchymal cell differentiation which could lead to excessive adipogenesis during development [24, 35]. Consistent with this scenario, we found that translin KO mice display increased fat mass and decreased fat-free mass as early as 7 weeks of age.…”

Section: Discussionsupporting

confidence: 90%

Deletion of translin (Tsn) induces robust adiposity and hepatic steatosis without impairing glucose tolerance

Shah

Johnson

et al. 2019

Int J Obes

View full text Add to dashboard Cite

Objective: Translin knockout (KO) mice display robust adiposity. Recent studies indicate that translin and its partner protein, trax, regulate the microRNA and ATM kinase signaling pathways, both of which have been implicated in regulating metabolism. In the course of characterizing the metabolic profile of these mice, we found that they display normal glucose tolerance despite their elevated adiposity. Accordingly, we investigated why translin KO mice display this paradoxical phenotype. Methods: To help distinguish between the metabolic effects of increased adiposity and those of translin deletion per se, we compared three groups: (1) wild-type (WT), (2) translin KO mice on a standard chow diet, and (3) adiposity-matched WT mice that were placed on a high-fat diet until they matched translin KO adiposity levels. All groups were scanned to determine their body composition and tested to evaluate their glucose and insulin tolerance. Plasma, hepatic and adipose tissue samples were collected and used for histological and molecular analyses. Results: Translin KO mice show normal glucose tolerance whereas adiposity-matched WT mice, placed on a high-fat diet, do not. In addition, translin KO mice display prominent hepatic steatosis that is more severe than that of adiposity-matched WT mice. Unlike adiposity-matched WT mice, translin KO mice display three key features that have been shown to reduce susceptibility to insulin resistance: increased accumulation of subcutaneous fat, increased levels of circulating adiponectin and decreased Tnfα expression in hepatic and adipose tissue. Conclusions: The ability of translin KO mice to retain normal glucose tolerance in the face of marked adipose tissue expansion may be due to the three protective factors noted above. Further studies aimed at defining the molecular bases for this combination of protective phenotypes may yield new approaches to limit the adverse metabolic consequences of obesity.

show abstract

Section: Discussionsupporting

confidence: 90%

Deletion of translin (Tsn) induces robust adiposity and hepatic steatosis without impairing glucose tolerance

Shah

Johnson

et al. 2019

Int J Obes

View full text Add to dashboard Cite

show abstract

“…Thus, it is conceivable that TN deletion from adipocyte or mesenchymal precursor cells may stimulate adipogenesis and contribute to the adiposity phenotype. This scenario would be consistent with the report that Tsn deletion increases differentiation of both mesenchymal stem cells and adipocyte precursor cells in vitro [30].…”

Section: Discussionsupporting

confidence: 93%

“…The ability of Tsn deletion or the Tsnax(E126A) point mutation to increase adiposity in the context of normal body weight suggests that it may act by biasing mesenchymal progenitor cell differentiation during development toward the adipocyte lineage and away from differentiation into osteocytes and myocytes. Furthermore, recent in vitro studies with mesenchymal stem cells support this hypothesis [30].…”

Section: Effect Of Global Conditional Deletion Of Tsn In Adulthood Omentioning

confidence: 87%

Genetic inactivation of the translin/trax microRNA-degrading enzyme phenocopies the robust adiposity induced by Translin (Tsn) deletion

Fu¹,

Shah²,

Li³

et al. 2020

Preprint

View full text Add to dashboard Cite

Objective: Deletion of Translin (Tsn) from mice induces an unusual metabolic profile characterized by robust adiposity, normal body weight and glucose tolerance.Translin (TN) protein and its partner, trax (TX), form the TN/TX microRNA-degrading enzyme. Since the microRNA system plays a prominent role in regulating metabolism, we reasoned that the metabolic profile displayed by Tsn KO mice might reflect dysregulation of microRNA signaling. Methods:To test this hypothesis, we inserted a mutation, E126A, in Tsnax, the gene encoding TX, that abolishes the microRNA-degrading enzymatic activity of the TN/TX complex. In addition, to help define the cell types that drive the adiposity phenotype, we have also generated mice with floxed alleles of Tsn or Tsnax.Results: Introduction of the E126A mutation in Tsnax does not impair expression of TN or TX proteins or their co-precipitation. Furthermore, these mice display selective increases in microRNAs that match those induced by Tsn deletion, confirming that this mutation in Tsnax inactivates the microRNA-degrading activity of the TN/TX complex. Mice homozygous for the Tsnax (E126A) mutation display a metabolic profile that closely mimics that of Tsn KO mice.Selective deletion of Tsn or Tsnax from either adipocytes or hepatocytes, two candidate cell types, does not phenocopy the elevated adiposity displayed by mice with constitutive Tsn deletion or the Tsnax(E126A) mutation. Furthermore, global, conditional deletion of Tsn in adulthood does not elicit increased adiposity.Conclusion: Taken together, these findings indicate that inactivation of the TN/TX microRNA-degrading enzyme during development is necessary to drive the robust adiposity displayed by Tsn KO mice.Recent studies have strongly implicated the microRNA system in regulating adipose tissue size and function [14][15][16]. For example, conditional deletion of Dicer from adipocytes inhibits lipogenesis in white adipocytes and produces severe depletion of white adipose tissue [17,18]. In previous studies, we have shown that the TN/TX complex can oppose the action of Dicer by degrading pre-microRNAs, thereby preventing their processing into mature microRNAs by Dicer [10]. Thus, these findings suggested that the adiposity displayed by Tsn KO mice could be attributed to increased microRNA signaling due to loss of the TN/TX microRNA-degrading enzyme. To test this hypothesis directly, we have taken advantage of recent studies which have

show abstract

“…Translin (TSN) is a DNA-binding protein that can form multimers with Translin-related factor X (TRAX) and modulates RNA processing and DNA repair. Translin was shown to restrict the proliferation and differentiation of mesenchymal cells [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics analysis of young and elderly skin with DIA mass spectrometry reveals new skin aging-related proteins

Liu

Wang

et al. 2020

Aging

View full text Add to dashboard Cite

Skin aging is a specific manifestation of the physiological aging process that occurs in virtually all organisms. In this study, we used data independent acquisition mass spectrometry to perform a comparative analysis of protein expression in volar forearm skin samples from of 20 healthy young and elderly Chinese individuals. Our quantitative proteomic analysis identified a total of 95 differentially expressed proteins (DEPs) in aged skin compared to young skin. Enrichment analyses of these DEPs (57 upregulated and 38 downregulated proteins) based on the GO, KEGG, and KOG databases revealed functional clusters associated with immunity and inflammation, oxidative stress, biosynthesis and metabolism, proteases, cell proliferation, cell differentiation, and apoptosis. We also found that GAPDH, which was downregulated in aged skin samples, was the top hub gene in a protein-protein interaction network analysis. Some of the DEPs identified herein had been previously correlated with aging of the skin and other organs, while others may represent novel age-related entities. Our non-invasive proteomics analysis of human epidermal proteins may guide future research on skin aging to help develop treatments for age-related skin conditions and rejuvenation.

show abstract

Translin modulates mesenchymal cell proliferation and differentiation in mice

Cited by 7 publications

References 20 publications

Deletion of translin (Tsn) induces robust adiposity and hepatic steatosis without impairing glucose tolerance

Deletion of translin (Tsn) induces robust adiposity and hepatic steatosis without impairing glucose tolerance

Genetic inactivation of the translin/trax microRNA-degrading enzyme phenocopies the robust adiposity induced by Translin (Tsn) deletion

Quantitative proteomics analysis of young and elderly skin with DIA mass spectrometry reveals new skin aging-related proteins

Contact Info

Product

Resources

About