The controversial role of tumor necrosis factor α in fibrotic diseases

Distler, Jörg H W; Schett, Georg; Distler, Oliver

doi:10.1002/art.23645

Cited by 101 publications

(73 citation statements)

References 52 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Actin polymerization is known to regulate the nuclear localization of the SRF cofactor, MKL (39), an effector of TGFβ, a cytokine which has been shown to be antagonistic to TNFα (40,41). Cell-geometry-dependent differential actin organization leads to differential MKL nuclear localization, with the RA cells having a significant amount of nuclear MKL, whereas CI cells have largely cytoplasmic MKL.…”

Section: Discussionmentioning

confidence: 99%

Cell geometry dictates TNFα-induced genome response

Mitra

Venkatachalapathy

Ratna

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Cells in physiology integrate local soluble and mechanical signals to regulate genomic programs. Whereas the individual roles of these signals are well studied, the cellular responses to the combined chemical and physical signals are less explored. Here, we investigated the cross-talk between cellular geometry and TNFα signaling. We stabilized NIH 3T3 fibroblasts into rectangular anisotropic or circular isotropic geometries and stimulated them with TNFα and analyzed nuclear translocation of transcription regulators -NFκB (p65) and MKL and downstream gene-expression patterns. We found that TNFα induces geometry-dependent actin depolymerization, which enhances IκB degradation, p65 nuclear translocation, nuclear exit of MKL, and sequestration of p65 at the RNA-polymerase-II foci. Further, global transcription profile of cells under matrix-TNFα interplay reveals a geometry-dependent gene-expression pattern. At a functional level, we find cell geometry affects TNFα-induced cell proliferation. Our results provide compelling evidence that fibroblasts, depending on their geometries, elicit distinct cellular responses for the same cytokine.cell geometry | TNFα | NFκB | gene expression

show abstract

Section: Discussionmentioning

confidence: 99%

Cell geometry dictates TNFα-induced genome response

Mitra

Venkatachalapathy

Ratna

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In addition, TGF-␤ was shown to promote the differentiation and accumulation of fibrocytes (6, 12) whereas aggregated IgG or serum amyloid P block differentiation (28,29). TNF can have pro-and anti-fibrotic effects (30) and, as a single agent, did not alter the numbers of human fibrocytes or their production of collagen I (8,27). Production of cytokines by CD4 ϩ T cells is regulated by the influx of Ca that interacts with calcineurin.…”

Section: In Contrast Activation Of Cd4 ؉ T Cells In the Presence Of mentioning

confidence: 99%

CD4⁺T cells control the differentiation of Gr1⁺monocytes into fibrocytes

Niedermeier

Reich

Gómez

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

209

219

View full text Add to dashboard Cite

“…He described that while TGF-a is an important player in regulating RIF as well as from other insults, TNF-a with or without TGF-a can play role in fibrosis, more importantly in certain cell types (66). In a nonradiation insult, induction of cardiac fibrosis in an experimental mouse model was correlated with increased serum level of TGF-a and decreased TNF-a (67).…”

Section: Potential Targets For Mitigation and Treatment Of Fibrosismentioning

confidence: 99%