Progranulin promotes tumour necrosis factor‐induced proliferation of suppressive mouse <scp>CD</scp>4<sup>+</sup> <scp>F</scp>oxp3<sup>+</sup> regulatory <scp>T</scp> cells

Ya, HU; Xiao, Haitao; Shi, Tingchen; Oppenheim, Joost J.; Chen, Xin

doi:10.1111/imm.12241

Cited by 27 publications

(32 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our analysis, PGRN caused impaired insulin signaling mainly through TNFR1 rather than TNFR2 in vitro. Several other groups also independently reproduced the binding of PGRN to TNFR1 and TNFR2 and the inhibitory effect of this binding on TNFA-induced effects (Jian et al 2013, Hu et al 2014. Our findings support the notion that PGRN is a key regulator of insulin resistance and that PGRN may mediate its effects, at least in part, by binding to TNF receptors.…”

Section: Discussionsupporting

confidence: 84%

Progranulin induces adipose insulin resistance and autophagic imbalance via TNFR1 in mice

Zhou¹,

Li²,

Liu³

et al. 2015

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of PGRN in vivo and the underlying role of progranulin in adipose insulin resistance involving the autophagy mechanism is not fully understood. In this study, mice treated with PGRN for 21 days exhibited the impaired glucose tolerance and insulin sensitivity, remarkable adipose autophagy as well as attenuated insulin signaling via inhibition of mammalian target of rapamycin (mTOR) pathway. Furthermore, blockade of tumor necrosis factor receptor 1 (TNFR1) by TNFR1BP-Fc injection resulted in the restoration of impaired insulin sensitivity and insulin signaling induced by PGRN. Consistent with these findings in vivo, PGRN treatment induced defective insulin signaling, abnormal autophagic and mitochondrial activity in cultured adipocytes, while such effects were nullified by the blockade of TNFR1. In addition, PGRN-deficient adipocytes were more refractory to tunicamycin-or dexamethasone-induced insulin resistance, indicating the causative role of the TNFR1 pathway in the action of PGRN. Collectively, our findings support the notion that PGRN is a key regulator of insulin resistance and that PGRN may mediate its effects, at least in part, by inducing autophagy via the TNFR1-dependent mechanism.

show abstract

Section: Discussionsupporting

confidence: 84%

Progranulin induces adipose insulin resistance and autophagic imbalance via TNFR1 in mice

Zhou¹,

Li²,

Liu³

et al. 2015

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…The effect of TNFα on regulation of Tregs purified from mice and humans remains to be highly controversial. The data from Chen lab suggest that TNFα promotes murine Treg activity in vitro [28], whereas in humans, TNFα inhibits the suppressive function of Tregs through negative regulation of Foxp3 expression [29; 30; 31; 32]. Our report that PGRN protects human Tregs from negative regulation by TNFα [20] also supported the concept that TNFα inhibits the suppressive function of Tregs.…”

Section: Discussionsupporting

confidence: 79%

“…PGRN significantly protects Treg function from a negative regulation by TNFα, assayed by IFNγ secretion, and also prevented the downregulation of Foxp3 by TNFα in Tregs [20]. In Discussion section of Chen paper, they speculated that the effect of PGRN on Treg suppression in our study is due to the inhibition of IFNγ secretion from Teffs directly [28]. This is wrong because PGRN was washed out after treatment of Tregs and PGRN was no present during the co-culture with Teffs [20].…”

Section: Discussionmentioning

confidence: 87%

See 1 more Smart Citation

Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity

et al. 2014

View full text Add to dashboard Cite

PGRN was previously reported to bind to TNF receptors (TNFR) and is therapeutic against inflammatory arthritis. Here we present further evidences demonstrating the PGRN inhibition of TNFα binding and activity, and clarifying the distinct mechanisms underlying TNFα inhibition between PGRN and classic TNFα-binding inhibitors. In addition, we present evidences indicating that three TNFR binding domains of PGRN act independently in binding to TNFR. Furthermore, changing the order of three TNFR-binding domains in Atsttrin, an PGRN-derived molecule composed of these TNFR-binding domains, does not affect its anti-inflammatory and anti-TNF activities in both collagen-induced inflammatory arthritis and human TNF-α transgenic mouse model. Taken together, these findings provide the additional molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various inflammatory diseases and conditions.

show abstract

“…20,22 Several other groups also independently reproduced the binding of PGRN to TNFR1 and TNFR2, and inhibitory effect of this binding on TNFa-induced effects. [53][54][55][56] Nevertheless, one recent study implied that the disturbance of the interaction between PGRN and TNFR2 abolished PGRN-mediated activation of Erk1/2 pathway. 53 These discrepancies with our results might be possibly because there is a different distribution between TNFR1 and TNFR2 in different cell types, and the role of PGRN in energy metabolism might be more complicated than expected.…”

Section: Discussionmentioning

confidence: 99%

Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner

Zhou

Liu

et al. 2015

Cell Cycle

View full text Add to dashboard Cite

Progranulin (PGRN) has recently emerged as an important regulator for glucose metabolism and insulin sensitivity. However, the direct effects of PGRN in vivo and the underlying mechanisms between PGRN and impaired insulin sensitivity are not fully understood. In this study, mice treated with PGRN for 21 d exhibited the impaired glucose tolerance and insulin sensitivity, remarkable ER stress as well as attenuated insulin signaling in liver and adipose tissue but not in skeletal muscle. Furthermore, treatment of mice with phenyl butyric acid (PBA), a chemical chaperone alleviating ER stress, resulted in a significant restoration of systemic insulin sensitivity and recovery of insulin signaling induced by PGRN. Consistent with these findings in vivo, we also observed that PGRN treatment induced ER stress, impaired insulin signaling in cultured hepatocytes and adipocytes, with such effects being partially nullified by blockade of PERK. Whereas PGRN-deficient hepatocytes and adipocytes were more refractory to palmitate-induced insulin resistance, indicating the causative role of the PERK-eIF2a axis of the ER stress response in action of PGRN. Collectively, our findings supported the notion that PGRN is a key regulator of insulin resistance and that PGRN may mediate its effects, at least in part, by inducing ER stress via the PERK-eIF2a dependent pathway.

show abstract

Progranulin promotes tumour necrosis factor‐induced proliferation of suppressive mouse CD4⁺ Foxp3⁺ regulatory T cells

Cited by 27 publications

References 32 publications

Progranulin induces adipose insulin resistance and autophagic imbalance via TNFR1 in mice

Progranulin induces adipose insulin resistance and autophagic imbalance via TNFR1 in mice

Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity

Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner

Contact Info

Product

Resources

About

Progranulin promotes tumour necrosis factor‐induced proliferation of suppressive mouse CD4+ Foxp3+ regulatory T cells

Cited by 27 publications

References 32 publications

Progranulin induces adipose insulin resistance and autophagic imbalance via TNFR1 in mice

Progranulin induces adipose insulin resistance and autophagic imbalance via TNFR1 in mice

Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity

Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner

Contact Info

Product

Resources

About

Progranulin promotes tumour necrosis factor‐induced proliferation of suppressive mouse CD4⁺ Foxp3⁺ regulatory T cells