Growth and differentiation factor 15 and NF‐κB expression in benign prostatic biopsies and risk of subsequent prostate cancer detection

Rybicki, Benjamin A.; Sadasivan, Sudha; Chen, Yalei; Kravtsov, Oleksandr; Palangmonthip, Watchareepohn; Arora, Kanika; Gupta, Nilesh; Williamson, Sean R.; Bobbitt, Kevin; Chitale, Dhananjay; Tang, Deliang; Rundle, Andrew; Iczkowski, Kenneth A.

doi:10.1002/cam4.3850

Cited by 15 publications

(7 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is important to note that in skeletal muscle tissue we were only able to detect the immature and non-cleaved form of GDF15 (pro-GDF15) and not the mature form, which is the one found in the circulation and considered the most active. Thus, we cannot rule out the possibility that SM-GDF15 (being an immature form) is not proportionally connected with the levels of c-GDF15 (therefore accounting for the missing association between the two forms), however, it is known that many other organs and tissues produce this protein, including prostate, kidney, lung, but also senescent cells and many types of cancers ( 13 , 26 , 58 – 60 ). Therefore, the level of c-GDF15 derives from the sum of all these contributions, reflecting the general health state of a subject rather than muscle health alone.…”

Section: Discussionmentioning

confidence: 98%

Different roles of circulating and intramuscular GDF15 as markers of skeletal muscle health

Chiariello,

Conte,

Rossetti

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

IntroductionGrowth Differentiation Factor 15 (GDF15) is a mitokine expressed in response to various stresses whose circulating levels increase with age and are associated with numerous pathological conditions, including muscle wasting and sarcopenia. However, the use of circulating GDF15 (c-GDF15) as a biomarker of sarcopenia is still debated. Moreover, the role of GDF15 intracellular precursor, pro-GDF15, in human skeletal muscle (SM-GDF15) is not totally understood. In order to clarify these points, the association of both forms of GDF15 with parameters of muscle strength, body composition, metabolism and inflammation was investigated.Methodsthe levels of c-GDF15 and SM-GDF15 were evaluated in plasma and muscle biopsies, respectively, of healthy subjects (HS) and patients with lower limb mobility impairment (LLMI), either young (<40 years-old) or old (>70 years-old). Other parameters included in the analysis were Isometric Quadriceps Strength (IQS), BMI, lean and fat mass percentage, Vastus lateralis thickness, as well as circulating levels of Adiponectin, Leptin, Resistin, IGF-1, Insulin, IL6, IL15 and c-PLIN2. Principal Component Analysis (PCA), Canonical Discriminant Analysis (CDA) and Receiving Operating Characteristics (ROC) analysis were performed.Resultsc-GDF15 but not SM-GDF15 levels resulted associated with decreased IQS and IGF-1 levels in both HS and LLMI, while only in LLMI associated with increased levels of Resistin. Moreover, in LLMI both c-GDF15 and SM-GDF15 levels were associated with IL-6 levels, but interestingly SM-GDF15 is lower in LLMI with respect to HS. Furthermore, a discrimination of the four groups of subjects based on these parameters was possible with PCA and CDA. In particular HS, LLMI over 70 years or under 40 years of age were discriminated based on SM-GDF15, c-GDF15 and Insulin levels, respectively.Conclusionour data support the idea that c-GDF15 level could be used as a biomarker of decreased muscle mass and strength. Moreover, it is suggested that c-GDF15 has a different diagnostic significance with respect to SM-GDF15, which is likely linked to a healthy and active state.

show abstract

Section: Discussionmentioning

confidence: 98%

Different roles of circulating and intramuscular GDF15 as markers of skeletal muscle health

Chiariello,

Conte,

Rossetti

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…The NF-κB family protein consists of homodimers and heterodimers formed by five subunits (p65, c-rel, RelB, p50, and p52). The most common heterodimer, p65/p50, is present in most cell types and is retained in an inactive form in the cytoplasm, then released to the nucleus activating the NF-κB signalling pathways [ 41 , 42 ]. Therefore, we explored the expression pattern of p65 in our experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

Role of Periostin and Nuclear Factor-κB Interplay in the Development of Diabetic Nephropathy

Abbad

Prakoura

Michon

et al. 2022

Cells

View full text Add to dashboard Cite

Diabetic nephropathy (DN) remains the most common reason for end-stage renal disease and a leading cause of kidney replacement therapy. Multifactorial pathophysiological mechanisms underlie the development of DN. Among the signalling pathways involved, nuclear factor-κB (NF-κB) plays a key role in pathogenesis triggering inflammation, oxidative stress and fibrosis. Recent evidence shows that periostin, a matricellular protein, is involved in the development of renal glomerular diseases through interaction with NF-κB signalling. The aim of the present study is to investigate the contribution of periostin and its interaction with NF-κB in DN development. To this end, we used the BTBR ob/ob mice model of diabetes type 2, and we applied transcriptomic analysis, immunostaining and methods quantifying protein and mRNA expressions. We found that increased periostin expression was correlated with decreased renal function, advanced stage renal damage and fibrosis, and NF-κB activation. Subsequently, we identified novel pathways and genes regulated by the NF-κB-periostin interaction which are involved in the mechanisms of progression of DN. Some of these genes, such as FGF1 and GDF15, have the potential to be new biomarkers and/or targets for the therapy of DN.

show abstract

“…Growth differentiation factor 15 (GDF‐15), also known as nonsteroidal anti-inflammatory drug-inducible gene (NAG)-1 or macrophage inhibitory cytokine (MIC)-1, is a member of the TGF-β superfamily proteins. GDF-15 is induced by cellular stress conditions and responds to microenvironment stimulators 86 , 87 . GDF-15 is dysregulated not only in epithelial cancer cells, but also in the tumor stroma 88 , and highly expressed GDF-15 is associated with worse clinical outcomes in prostate cancer 89 , 90 .…”

Section: Introductionmentioning

confidence: 99%

Tumor microenvironment heterogeneity an important mediator of prostate cancer progression and therapeutic resistance

Wang

Cheng

2022

npj Precis. Onc.

View full text Add to dashboard Cite

Prostate cancer is characterized by a high degree of heterogeneity, which poses a major challenge to precision therapy and drug development. In this review, we discuss how nongenetic factors contribute to heterogeneity of prostate cancer. We also discuss tumor heterogeneity and phenotypic switching related to anticancer therapies. Lastly, we summarize the challenges targeting the tumor environments, and emphasize that continued exploration of tumor heterogeneity is needed in order to offer a personalized therapy for advanced prostate cancer patients.

show abstract

Growth and differentiation factor 15 and NF‐κB expression in benign prostatic biopsies and risk of subsequent prostate cancer detection

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 15 publications

References 46 publications

Different roles of circulating and intramuscular GDF15 as markers of skeletal muscle health

Different roles of circulating and intramuscular GDF15 as markers of skeletal muscle health

Role of Periostin and Nuclear Factor-κB Interplay in the Development of Diabetic Nephropathy

Tumor microenvironment heterogeneity an important mediator of prostate cancer progression and therapeutic resistance

Contact Info

Product

Resources

About