Primary cilia are dysfunctional in obese adipose-derived mesenchymal stem cells

Ritter, Andreas; Friemel, Alexandra; Kreis, Nina-Naomi; Hoock, SC; Roth, Susanne; Kielland-Kaisen, Ulrikke; Brüggmann, Dörthe; Solbach, Christine; Louwen, Frank; Yuan, Juping

doi:10.1055/s-0038-1671441

Cited by 11 publications

(26 citation statements)

References 23 publications

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“…Furthermore, it is crucial to understand why/how ASCs alter their functions in obesity. Recently, we have reported that, compared with control ASCs, obese ASCs display defective primary cilia, which are shortened and unable to properly respond to various stimuli . Impaired primary cilia compromise ASC functionalities like differentiation and motility .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we have reported that, compared with control ASCs, obese ASCs display defective primary cilia, which are shortened and unable to properly respond to various stimuli . Impaired primary cilia compromise ASC functionalities like differentiation and motility . Further work is warranted to investigate the biology of ASCs in normal and obese adipose tissues.…”

Section: Discussionmentioning

confidence: 99%

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Insight into the development of obesity: functional alterations of adipose‐derived mesenchymal stem cells

et al. 2018

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Obesity is associated with a variety of disorders including cardiovascular diseases, diabetes mellitus and cancer. Obesity changes the composition and structure of adipose tissue, linked to pro-inflammatory environment, endocrine/metabolic dysfunction, insulin resistance and oxidative stress. Adipose-derived mesenchymal stem cells (ASCs) have multiple functions like cell renewal, spontaneous repair and homeostasis in adipose tissue. In this review article, we have summarized the recent data highlighting that ASCs in obesity are defective in various functionalities and properties including differentiation, angiogenesis, motility, multipotent state, metabolism and immunomodulation. Inflammatory milieu, hypoxia and abnormal metabolites in obese tissue are crucial for impairing the functions of ASCs. Further work is required to explore the precise molecular mechanisms underlying its alterations and impairments. Based on these data, we suggest that deregulated ASCs, possibly also other mesenchymal stem cells, are important in promoting the development of obesity. Restoration of ASCs/mesenchymal stem cells might be an additional strategy to combat obesity and its associated diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Insight into the development of obesity: functional alterations of adipose‐derived mesenchymal stem cells

et al. 2018

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“…RNA extraction and real-time PCR were performed as described (Kreis et al, 2019a;Ritter et al, 2018).…”

Section: Cell Viability Wound Healing/migration Invasion Assay Andmentioning

confidence: 99%

RITA modulates cell migration and invasion by affecting focal adhesion dynamics

et al. 2019

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RITA, the RBP‐J interacting and tubulin‐associated protein, has been reported to be related to tumor development, but the underlying mechanisms are not understood. Since RITA interacts with tubulin and coats microtubules of the cytoskeleton, we hypothesized that it is involved in cell motility. We show here that depletion of RITA reduces cell migration and invasion of diverse cancer cell lines and mouse embryonic fibroblasts. Cells depleted of RITA display stable focal adhesions (FA) with elevated active integrin, phosphorylated focal adhesion kinase, and paxillin. This is accompanied by enlarged size and disturbed turnover of FA. These cells also demonstrate increased polymerized tubulin. Interestingly, RITA is precipitated with the lipoma‐preferred partner (LPP), which is critical in actin cytoskeleton remodeling and cell migration. Suppression of RITA results in reduced LPP and α‐actinin at FA leading to compromised focal adhesion turnover and actin dynamics. This study identifies RITA as a novel crucial player in cell migration and invasion by affecting the turnover of FA through its interference with the dynamics of actin filaments and microtubules. Its deregulation may contribute to malignant progression.

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“…Importantly, the Hh signalling pathway is deficient in obese ASCs, accompanied by reduced expression of its related genes like GLI1, PTCH1, SMO and the homeobox protein NANOG. The latter is known as a direct target of the Hh pathway in glioma stem cells and ASCs (63,64). These transcription factors are associated with the self-renewal of stem cells (65,66), and thus, altered expression of these genes may explain reduced undifferentiated multipotency of ASCs in the obese state (16,67).…”

Section: Dysfunctional Primary Cilia In Obese Adipose-derived Mesenchmentioning

confidence: 99%

Deficient primary cilia in obese adipose‐derived mesenchymal stem cells: obesity, a secondary ciliopathy?

2018

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Obesity alters the composition, structure and function of adipose tissue, characterized by chronic inflammation, insulin resistance and metabolic dysfunction. Adipose-derived mesenchymal stem cells (ASCs) are responsible for cell renewal, spontaneous repair and immunomodulation in adipose tissue. Increasing evidence highlights that ASCs are deficient in obesity, and the underlying mechanisms are not well understood. We have recently shown that obese ASCs have defective primary cilia, which are shortened and unable to properly respond to stimuli. Impaired cilia compromise ASC functions. This work suggests an intertwined connection of obesity, defective cilia and dysfunctional ASCs. We have here discussed the current data regarding defective cilia in various cell types in obesity. Based on these observations, we hypothesize that obesity, a systemic chronic metainflammation, could impair cilia in diverse ciliated cells, like pancreatic islet cells, stem cells and hypothalamic neurons, making these critical cells dysfunctional by shutting down their signal sensors and transducers. In this context, obesity may represent a secondary form of ciliopathy induced by obesity-related inflammation and metabolic dysfunction. Reactivation of ciliated cells might be an alternative strategy to combat obesity and its associated diseases.

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Primary cilia are dysfunctional in obese adipose-derived mesenchymal stem cells

Cited by 11 publications

References 23 publications

Insight into the development of obesity: functional alterations of adipose‐derived mesenchymal stem cells

Insight into the development of obesity: functional alterations of adipose‐derived mesenchymal stem cells

RITA modulates cell migration and invasion by affecting focal adhesion dynamics

Deficient primary cilia in obese adipose‐derived mesenchymal stem cells: obesity, a secondary ciliopathy?

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