Mechanisms of TGF-β-mediated apoptosis

Schuster, Norbert; Krieglstein, Kerstin

doi:10.1007/s00441-001-0479-6

Cited by 384 publications

(275 citation statements)

References 84 publications

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“…Although some studies indicate that TGF-β can both prevent and induce cell injury under different conditions depending on the specific paradigm (Bottner et al, 2000;, many other studies show that TGF-β is able to induce apoptosis and that Akt and downstream signaling intermediates block TGF-β induction of cell death (Samatar et al, 2002;Schuster and Krieglstein 2002). In the current study, increased glucose and TGF-β1 or TGF-β2 in combination produced greater neuronal injury in embryonic DRG than TGF-β used alone.…”

Section: Discussionmentioning

confidence: 99%

“…TGF-β comprises a family of cytokine growth factors that have several functions in the areas of cellular development, differentiation, extra cellular matrix formation and apoptosis (Lin and Moustakas 1994;Schuster and Krieglstein 2002). It has been generally accepted that functions of TGF-β family members may vary depending on cellular status and cell types.…”

Section: Introductionmentioning

confidence: 99%

“…In neuronal tissues, it is clear that TGF-βs play a neurotrophic role in some situations (Chalazonitis et al, 1992;Krieglstein et al, 1995;Martinou et al, 1990;Poulsen et al, 1994), while they elicit cell-death-inducing effects in other situations Schuster and Krieglstein 2002). However, the exact role of various isoforms of TGF-β and its functions are not understood in the peripheral nervous system or in diabetic neuropathy.…”

Section: Introductionmentioning

confidence: 99%

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Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Anjaneyulu

Berent-Spillson

Inoue

et al. 2008

Experimental Neurology

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The mechanism/s leading to diabetic neuropathy are complex. Transforming growth factor-β1 (TGF-β1) has been associated with diabetic nephropathy and retinopathy but not neuropathy. In this study, changes in TGF-β isoforms were examined in-vivo and in-vitro. Two groups of animals, streptozotocin diabetic with neuropathy and non-diabetic controls were examined at 4 weeks (n=10/ group) and 12 weeks (n=8/group). In diabetic DRG using quantitative real-time PCR (QRT-PCR), TGF-β1 and TGF-β2 mRNA, but not TGF-β3, was increased at 4 and 12 weeks. In sciatic nerve TGF-β3 mRNA was primarily increased. Immunohistochemistry (DRG) and immunoblotting (sciatic nerve) showed similar differential protein expression. In sciatic nerve TGF-β formed homoand heterodimers, of which β 2 /β 3 , β 1 /β 1 , and β 1 /β 3 were significantly increased, while that of the TGF-β 2 /β 2 homodimer was decreased, in diabetic compared to non-diabetic rats. In-vitro, pretreatment of embryonic DRG with TGF-β neutralizing antibody prevents the increase in total TGF-β protein observed with high glucose using immunoblotting. In high glucose conditions, combination with TGF-β2 > β1 increases the percent of cleaved caspase-3 compared to high glucose alone and TGF-β neutralizing antibody inhibits this increase. Furthermore, consistent with the findings in diabetic DRG and nerve, TGF-β isoforms applied directly in vitro reduce neurite outgrowth, and this effect is partially reversed by TGF-β neutralizing antibody. These findings implicate upregulation of TGF-β in experimental diabetic peripheral neuropathy and indicate a novel mechanism of cellular injury related to elevated glucose levels. In combination, these findings indicate a potential new target for treatment of diabetic peripheral neuropathy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Anjaneyulu

Berent-Spillson

Inoue

et al. 2008

Experimental Neurology

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“…Three (ER-a, ER-b and AR) of 4 steroid receptors, which we found in the current study to have higher expression after RT, were found previously to have an ability to inactivate TGF-b antiproliferative signaling pathway by inhibition of Smad3. [35][36][37][38][39] Interestingly, ER-b was the only steroid receptor to be upregulated in prostate adenocarcinoma epithelial cells after RT. We have demonstrated previously that ER-b expression is associated positively with Gleason score and primary Gleason grade with higher levels expressed in higher grade tumors.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of steroid receptors in prostate tissues before and after radiation therapy for prostatic adenocarcinoma

Torlakovic

Lilleby²,

Berner

et al. 2005

Intl Journal of Cancer

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The expression, distribution and the role of steroid receptors in benign and malignant untreated prostate tissues is well recognized, however, the status of steroid receptors in prostate after radiotherapy (RT) for adenocarcinoma has not yet been studied fully. Immunohistochemical evaluation of androgen receptor (AR), estrogen receptor-alpha (ER-a), estrogen receptor-beta (ER-b), and progesterone receptor (PR) was carried out in prostate needle biopsies obtained before and after radiotherapy from 60 patients with adenocarcinoma. The ER-b transcripts were also studied by RT-PCR in LNCaP prostate carcinoma cell line before and 24 hr after c-irradiation at 0.5 Gy and 8.0 Gy. Significantly higher level of ER-b expression was found in post-radiation samples of prostate adenocarcinoma and benign epithelium. After RT, all steroid receptors were upregulated in prostatic stroma. Tumor AR expression did not change significantly. Although a positive association between AR and ER-b expression was observed in pretreatment prostate adenocarcinoma, it was lost after RT suggesting that these 2 steroid receptors respond differently to RT. High levels of pretreatment tumor ER-b were associated with local recurrence after RT and decreased biochemical recurrence-free survival (p 5 0.028). LNCaP cell line that expressed no ER-b mRNA before c-irradiation, clearly expressed ER-b mRNA 24 hr after 0.5 Gy and 8.0 Gy. Upregulation of all steroid receptors in the prostate stroma and upregulation of ER-b in the tumor epithelium after RT, may represent a protective tissue response to radiation-induced tissue injury. Although stromal AR was doubled after RT, the tumor and benign epithelium expression of AR seemed resistant to change by RT. ' 2005 Wiley-Liss, Inc.

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“…SMAD3 plus the SMAD3-inhibitor SMAD7 were included because they are transcriptional modulators activated by TGFb1 and, in the case of SMAD7, by EGF, and because SMAD3 interacts directly with Fas. We also included CTGF, as this gene may also be involved in smad-mediated TGFb-induced cell death [18,39]. Real-time RT-PCR was performed using the ABI PRISM1 7900 HT sequence detection system with primer sets (TaqMan1 gene expression assays) supplied by Applied Biosystems (Foster City, CA).…”

Section: Methodsmentioning

confidence: 99%

Fas Death Pathway in Sarcomas Correlates with Epidermal Growth Factor Transcription

Joyner

Aboulafia

Damron

et al. 2008

Clin Orthop Relat Res

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Modulation of apoptosis may influence sarcoma pathogenesis and/or aggressiveness. The Fas death pathway, mediated by FasL or TGFb, is one of two apoptotic pathways. Recent studies report that EGF can modulate TGFb and/or FasL expression/activity; thus, EGF has the potential to influence activation of the Fas pathway. EGF is not always detectable in mesenchymal tumors; therefore, we hypothesized EGF would define which Fas ligand predominates. We assayed 57 surgically removed human sarcomas for 10 genes involved in the Fas pathway. Skeletal muscle biopsies from eight patients served as controls. Sample transcripts were detected by real-time RT-PCR. We attempted to identify relevant predictor variables. The 57 sarcomas were segregated into two categories defined by EGF mRNA content: (1) 23 tumors with EGF concentrations that approximated muscle EGF transcript levels (high-EGF tumors); and (2) 34 tumors that either lacked EGF mRNA, or whose mRNA levels were very low and frequently undetected by PCR (low-EGF tumors). TGFb1 expression best predicted Fas transcript concentrations in the 34 low-EGF sarcomas, while FasL predicted Fas mRNA levels in the remaining 23 high-EGF sarcomas. The results suggest ligand activity in the Fas death pathway correlates with EGF transcription in sarcomas.

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Mechanisms of TGF-β-mediated apoptosis

Cited by 384 publications

References 84 publications

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Differential expression of steroid receptors in prostate tissues before and after radiation therapy for prostatic adenocarcinoma

Fas Death Pathway in Sarcomas Correlates with Epidermal Growth Factor Transcription

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