Upregulation of mRNA expression of MCP-1 by TGF-β1 in fibroblast cells from Peyronie’s disease

Szardening-Kirchner, Carolin; Konrad, Lutz; Hauck, Ekkehard W.; Haag, Simone M.; Eickelberg, Oliver; Weidner, W.

doi:10.1007/s00345-008-0320-x

Cited by 27 publications

(21 citation statements)

References 33 publications

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“…73 SMAD7 expression is normally increased following TGFβ1-mediated signaling, and SMAD7 antagonizes TGFβ1 signaling in multiple ways including dephosphorylation and resulting inactivation of the type 1 TGF β 1 receptor (TGFB1R), recruitment of SMAD2/3 and the ubiquitination and eventual degradation of the TGFβ1 type 1 receptor. 74–76 Although subsequent work by Szardening-Kirchner et al 52 did not observe decreased SMAD7 expression following incubation of PD fibroblasts with recombinant TGFβ1, gene expression levels of SMAD2-4 did not change despite fibroblast stimulation with TGFβ1, suggesting potential dysfunction of SMAD7-mediated recruitment of SMAD2/3. The potential under-expression or loss of function of SMAD7 may therefore remove an important checkpoint in the inflammatory cascade, predisposing to PD.…”

Section: Gene Expression Profilesmentioning

confidence: 86%

“…51 Higher levels of MCP-1 mRNA have been observed in PD plaque-derived fibroblasts when compared to fibroblasts derived from normal TA following incubation with recombinant TGFβ1. 52 Lin et al exposed three types of fibroblasts to TGFβ1 – PD plaque-derived fibroblasts, non-plaque derived fibroblasts from patients with PD, and fibroblasts from the TA of patients without PD – and subsequently measured MCP-1 expression. 53 The highest levels of MCP-1 expression were found in PD plaque-derived fibroblasts using immunohistochemistry, followed by non-plaque derived fibroblasts from the same man, and then in fibroblasts from men without PD.…”

Section: Gene Expression Profilesmentioning

confidence: 99%

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The Genetic Basis of Peyronie Disease: A Review

Herati

Pastuszak

2016

Sexual Medicine Reviews

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Introduction Peyronie’s disease (PD) is progressive fibrotic disorder of the penile tunica albuginea that results in fibrotic penile plaques and may lead to penile deformity. Characterized by aberrant fibrosis resulting in part from persistence of myofibroblasts as well as altered gene expression, the molecular factors underpinning Peyronie’s disease and other related fibrotic diatheses are just being elucidated. A genetic link to PD was first identified using pedigree analyses three decades ago. However, the specific genetic factors that predispose patients to aberrant fibrosis remain unknown, and the relationships between these fibrotic conditions and other heritable diseases, including malignancy, are uncharacterized. Aim To review the current landscape linking molecular and genetic factors to aberrant fibrosis in PD as well as related fibrotic diatheses, including Dupuytren’s disease. Methods Review and evaluation of the literature from 1970 to present examining the genetic factors associated with PD. Main Outcome Measures Data describing the genetic factors associated with PD. Results We describe the known structural chromosomal abnormalities and single nucleotide polymorphisms associated with fibrotic diatheses, and discuss the spectrum of differential gene expression data comparing normal tissues and those derived from men with Peyronie’s or Dupuytren’s diseases. Finally, we discuss epigenetic mechanisms that may regulate gene expression and alter predisposition to fibrosis. Conclusion Although our current understanding of the genetic factors associated with PD are limited, significant advances have been made over the last three decades. Further research is necessary to provide a more comprehensive understanding of the landscape of genetic factors responsible for the development of PD.

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Section: Gene Expression Profilesmentioning

confidence: 86%

Section: Gene Expression Profilesmentioning

confidence: 99%

The Genetic Basis of Peyronie Disease: A Review

Herati

Pastuszak

2016

Sexual Medicine Reviews

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“…CoQ10 prevents nitrosative stress by inhibition of excess nitric oxide radical production, and it participates in vitamin E and C regeneration [91, 92]. CoQ10 has a strong anti-inflammatory and antifibrotic activity, producing a decrease of proinflammatory cytokines TNF- α , IL-6, TGF-ß1, and monocyte chemoattractant protein-1 (MCP-1), one of the cytokines that regulate migration and infiltration of monocytes-macrophages; furthermore, higher MCP-1 expression was found in PD-fibroblasts [93]. In addition, CoQ10 decreases gene expression of IL-1 β , NF- κ B, and iNOS [94].…”

Section: Pathophysiology Of Peyronie's' Disease (Figure 1)mentioning

confidence: 99%

Recent Pathophysiological Aspects of Peyronie’s Disease: Role of Free Radicals, Rationale, and Therapeutic Implications for Antioxidant Treatment—Literature Review

Paulis

Romano²,

Paulis

et al. 2017

Advances in Urology

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Peyronie's disease (PD) is a chronic inflammation of tunica albuginea of the corpora cavernosa that causes an inelastic plaque resulting in penis deformation. Although its etiology is not completely known, there is general consensus that PD is genetically transmitted and secondary to penile trauma. In recent years, numerous studies demonstrated the role played by oxidative stress in PD pathogenesis, and other studies have described successful use of antioxidants in PD treatment. Oxidative stress is an integral part of this disease, influencing its progression. In the early stages of PD, the inflammatory infiltrate cells produce high quantities of free radicals and proinflammatory and profibrotic cytokines, with consequent activation of transcription factor NF-κB. While conservative therapies commonly used in the early stages of PD include oral substances (Potaba, tamoxifen, colchicine, and vitamin E), intralesional treatment (verapamil, interferon, steroids, and more recently collagenase clostridium histolyticum-Xiaflex), and local physical treatment (iontophoresis, extracorporeal shock wave therapy, and penile extender), the significant results obtained by emerging treatments with the antioxidants cited in this article suggest these therapeutic agents interfere at several levels with the disease's pathogenetic mechanisms. Antioxidants therapy outcomes are interesting for good clinical practice and also confirm the fundamental role played by oxidative stress in PD.

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“…Many factors can activate the production of MCP-1, such as LPS, TGF-β1 and angiotensin. TGF-β1 is an important immunomodulatory cytokine which can significantly stimulate the expression of MCP-1 in fibroblast cells [41]. LPS can induce MCP-1 up-regulation by the activated NF-κB signaling pathway in fibrocyte [42]; the inhibition of this pathway results in a strong decrease in vitro [43].…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-κB pathway

Wang

et al. 2012

Lipids Health Dis

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BackgroundAtherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. In recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. LPS can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. Although LPS increases neointimal via TLR4 activation has been reported, how LPS augments atherogenesis through acting on adventitial fibroblasts is still unknown. Here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (LPS) to imitate inflammatory conditions.ResultsIn our study, LPS enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (ADRP) as the silencing of ADRP abrogated lipid deposition in LPS-activated adventitial fibroblasts. In addition, pre-treatment with anti-Toll-like receptor 4 (TLR4) antibody diminished the LPS-induced lipid deposition and ADRP expression. Moreover, LPS induced translocation of nuclear factor-κB (NF-κB), which could markedly up-regulate lipid deposition as pre-treatment with the NF-κB inhibitor, PDTC, significantly reduced lipid droplets. In addition, the lowering lipid accumulation was accompanied with the decreased ADRP expression. Furthermore, LPS-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (MCP-1), compared with transforming growth factor-β1 (TGF-β1).ConclusionsTaken together, these results suggest that LPS promotes lipid accumulation via the up-regulation of ADRP expression through TLR4 activated downstream of NF-κB in adventitial fibroblasts. Increased levels of MCP-1 released from LPS-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. Here, our study provides a new explanation as to how bacterial infection contributes to the pathological process of atherosclerosis.

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Upregulation of mRNA expression of MCP-1 by TGF-β1 in fibroblast cells from Peyronie’s disease

Abstract: In conclusion, analysis of MCP-1 expression might be a useful marker for Peyronie's disease.

Cited by 27 publications

References 33 publications

The Genetic Basis of Peyronie Disease: A Review

The Genetic Basis of Peyronie Disease: A Review

Recent Pathophysiological Aspects of Peyronie’s Disease: Role of Free Radicals, Rationale, and Therapeutic Implications for Antioxidant Treatment—Literature Review

Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-κB pathway

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