Cardiotrophin-1: A multifaceted cytokine

López-Yoldi, Miguel; Moreno-Aliaga, María J.; Bustos, Matilde

doi:10.1016/j.cytogfr.2015.07.009

Cited by 50 publications

(61 citation statements)

References 129 publications

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“…Specifically, we show that baseline CT‐1 gene expression levels were able to predict final 50% and 47% of post intervention insulin and HOMA index values, respectively. The research work on CT‐1 and glucose metabolism in human obese subjects is not conclusive . But, recent in vitro and in vivo studies indicated that CT‐1 plays an important protective role in beta‐cell viability, and also improves glucose‐stimulated insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, recent animal studies suggest that cardiotrophin‐1 (CT‐1) could be a key regulator of energy homeostasis, controlling glucose and lipid metabolism, but results in human obese subjects are scarce. The aim of this work was to examine changes in CT‐1, IL‐6, TNF‐α serum, and PBMC transcript levels after a lifestyle intervention in obese children and to assess their potential association with glucose metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Serum and gene expression levels of CT-1, IL-6, and TNF-α after a lifestyle intervention in obese children

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum and gene expression levels of CT-1, IL-6, and TNF-α after a lifestyle intervention in obese children

et al. 2017

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“…The effect of CT‐1 is probably because of its capacity to target multiple mechanisms involved in the development of UUO‐induced renal fibrosis, including epithelial tubular cell apoptosis, monocyte‐macrophage infiltration, abnormal deposition of ECM components and tubule‐interstitial inflammation . During the development of renal fibrosis, tubular cell apoptosis plays a key role promoting the progression of disease in terms of contributing to the inflammatory response and regulating fibroblasts abundance .…”

Section: Discussionmentioning

confidence: 99%

Cardiotrophin‐1 opposes renal fibrosis in mice: Potential prevention of chronic kidney disease

et al. 2019

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Aim Chronic kidney disease is characterized by tubulointerstitial fibrosis involving inflammation, tubular apoptosis, fibroblast proliferation and extracellular matrix accumulation. Cardiotrophin‐1, a member of the interleukin‐6 family of cytokines, protects several organs from damage by promoting survival and anti‐inflammatory effects. However, whether cardiotrophin‐1 participates in the response to chronic kidney injury leading to renal fibrosis is unknown. Methods We hypothesized and assessed the potential role of cardiotrophin‐1 in a mice model of tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO). Results Three days after UUO, obstructed kidneys from cardiotrophin‐1−/− mice show higher expression of inflammatory markers IL‐1β, Cd68, ICAM‐1, COX‐2 and iNOs, higher activation of NF‐κB, higher amount of myofibroblasts and higher severity of tubular damage and apoptosis, compared with obstructed kidneys from wild‐type littermates. In a later stage, obstructed kidneys from cardiotrophin‐1−/− mice show higher fibrosis than obstructed kidneys from wild‐type mice. Interestingly, administration of exogenous cardiotrophin‐1 prevents the increased fibrosis resulting from the genetic knockout of cardiotrophin‐1 upon UUO, and supplementation of wild‐type mice with exogenous cardiotrophin‐1 further reduces the renal fibrosis induced by UUO. In vitro, renal myofibroblasts from cardiotrophin‐1−/− mice have higher collagen I and fibronectin expression and higher NF‐κB activation than wild‐type cells. Conclusions Cardiotrophin‐1 participates in the endogenous response that opposes renal damage by counteracting the inflammatory, apoptotic and fibrotic processes. And exogenous cardiotrophin‐1 is proposed as a candidate for the treatment and prevention of chronic renal fibrosis.

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“…CT-1 has been reported to exert a plethora of pleiotropic effects on different tissues and cell types. Regarding its role in inflammation, CT-1 has been described as being able to induce acute phase-response proteins (1), and its protective role has been proven in a variety of experimental models of tissue damage, decreasing the levels of TNF-a (4,27,28). Our results, which are in line with the role of some gp130 cytokines in the response of LPS (29,30), show that the absence of CT-1 has effects on the levels of proinflammatory cytokines and that this function cannot be compensated by other cytokines.…”

Section: Discussionmentioning

confidence: 99%

Cardiotrophin‐1 is an anti‐inflammatory cytokine and promotes IL‐4–induced M2 macrophage polarization

et al. 2019

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Macrophages play a central role in tissue remodeling, repair, and resolution of inflammation. Macrophage polarization to Ml or M2 activation status may determine the progression or resolution of the inflammatory response. We have previously reported that cardiotrophin‐1 (CT‐1) displays both cytoprotective and metabolic activities. The role of CT‐1 in inflammation remains poorly understood. Here, we employed recombinant CT‐1 (rCT‐1) and used CT‐1–null mice and myeloid‐specif ic CT‐1 transgenic mice to investigate whether CT‐1 might play a role in the modulation of the inflammatory response. We observed that CT‐1 deficiency was associated with enhanced release of inflammatory mediators and with stronger activation of NF‐κB in response to LPS, whereas the inflammatory response was attenuated in CT‐1 transgenic mice or by administering rCT‐1 to wild‐type animals prior to LPS challenge. We found that CT‐1 promoted IL‐6 expression only by nonhematopoietic cells, whereas LPS up‐regulated IL‐6 expression in both hematopoietic and nonhematopoietic cells. Notably, rCT‐1 inhibited LPS‐mediated soluble IL‐6R induction. Using IL‐6−/− mice, we showed that rCT‐1 inhibited LPS‐induced TNF‐α and IFN‐γ response in an IL‐6–independent manner. Importantly, we demonstrated that CT‐1 primes macrophages for IL‐4–dependent M2 polarization by inducing IL‐4 receptor expression. Mechanistic analyses showed that the signal transducer and activator of transcription 3–suppressor of cytokine signaling 3 axis mediates this effect. Our findings support the notion that CT‐1 is a critical regulator of inflammation and suggest that rCT‐1 could be a molecule with potential therapeutic application in inflammatory conditions.—Carneros, D., Santamaría, E. M., Larequi, E., Vélez‐Ortiz, J. M., Reboredo, M., Mancheño, U., Perugorria, M. J., Navas, P., Romero‐Gómez, M., Prieto, J., Hervás‐Stubbs, S., Bustos, M. Cardiotrophin‐1 is an anti‐inflammatory cytokine and promotes IL‐4–induced M2 macrophage polarization. FASEB J. 33, 7578–7587 (2019). http://www.fasebj.org

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Cardiotrophin-1: A multifaceted cytokine

Cited by 50 publications

References 129 publications

Serum and gene expression levels of CT-1, IL-6, and TNF-α after a lifestyle intervention in obese children

Serum and gene expression levels of CT-1, IL-6, and TNF-α after a lifestyle intervention in obese children

Cardiotrophin‐1 opposes renal fibrosis in mice: Potential prevention of chronic kidney disease

Cardiotrophin‐1 is an anti‐inflammatory cytokine and promotes IL‐4–induced M2 macrophage polarization

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