Autocrine expression of activated transforming growth factor-β1 induces apoptosis in normal rat liver

Schrum, Laura W.; Bird, Mark A.; Salcher, Olga; Burchardt, Elmar R.; Grisham, Joe W.; Brenner, David A.; Rippe, Richard A.; Behrns, Kevin E.

doi:10.1152/ajpgi.2001.280.1.g139

Cited by 37 publications

(41 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that the release of TGF-β1 from lacerated muscle can induce the pathological differentiation of marrow-derived stem cells and other types of muscle cells (Li et al 2004). The continued upregulation of TGF-β1, via an autocrine mechanism, not only contributed to the infiltration of lymphocytes, but also triggered muscle cells to differentiate into fibroblasts and underwent atrophy during muscle healing, and had effects in various other types of cells, including cardiomyocytes and hepatocytes (Taimor et al 1999;Schrum et al 2001). TGF-β1 can induce collagen deposition by increasing synthesis of most matrix proteins and decreasing the production of matrix degrading proteases via the p38 MAPK pathway (RodriguezBarbero et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Expression of TGF-β1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice

Liu

Tang

Chen

et al. 2016

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Injury to the recurrent laryngeal nerve often leads to permanent vocal cord paralysis, which has a significant negative impact on the quality of life. Long-term denervation can induce laryngeal muscle fibrosis，which obstructs the muscle recovery after laryngeal reinnervation. However, the mechanisms of fibrosis remain unclear. In this study, we aimed to analyze the changes in the expression of fibrosis-related factors, including transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in denervated skeletal muscles using a mouse model of accessory nerve transection. Because of the small size, we used sternocleidomastoid muscles instead of laryngeal muscles for denervation experiments. Masson's trichrome staining showed that the grade of atrophy and fibrosis of muscles became more severe with time, but showed a plateau at 4 weeks after denervation, followed by a slow decrease. Quantitative assessment and immunohistochemistry showed that TGF-β1 expression peaked at 1 week after denervation (p < 0.05) and was maintained at its high level until 4 weeks. CTGFand α-SMA-positive muscle cells were detected at 1 week after denervation, peaked at 2 weeks (p < 0.05), and remained at high levels with a subsequent slight decrease for 3-4 weeks. These results suggest that TGF-β1 and CTGF may be involved in the process of denervated skeletal muscle fibrosis. They may induce the differentiation of myoblasts into myofibroblasts, as characterized by the activation of α-SMA. These findings may provide insights on key pathological processes in denervated skeletal muscle fibrosis and develop novel therapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of TGF-β1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice

Liu

Tang

Chen

et al. 2016

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

“…This effectively results in enhanced cell proliferation and reduced cell death [55]. Livers in rats in which TGF-β is overexpressed and cell proliferation is inhibited cannot regenerate after partial hepatectomy [56], indicating that enhanced cell proliferation and reduced apoptosis is of high importance for liver regeneration. Another good example, demonstrating the coordinated control of cell numbers and organ size by cell proliferation and apoptosis, was shown in tumor-promoting agent treatment experiment in liver and kidney.…”

Section: Coordination Of Cell Proliferation and Cell Death In Size Comentioning

confidence: 99%

Molecular mechanism of size control in development and human diseases

Yang

2011

Cell Res

View full text Add to dashboard Cite

How multicellular organisms control their size is a fundamental question that fascinated generations of biologists. In the past 10 years, tremendous progress has been made toward our understanding of the molecular mechanism underlying size control. Original studies from Drosophila showed that in addition to extrinsic nutritional and hormonal cues, intrinsic mechanisms also play important roles in the control of organ size during development. Several novel signaling pathways such as insulin and Hippo-LATS signaling pathways have been identified that control organ size by regulating cell size and/or cell number through modulation of cell growth, cell division, and cell death. Later studies using mammalian cell and mouse models also demonstrated that the signaling pathways identified in flies are also conserved in mammals. Significantly, recent studies showed that dysregulation of size control plays important roles in the development of many human diseases such as cancer, diabetes, and hypertrophy.

show abstract

“…As described previously, caspase-3 and caspase-8 activities were determined with the substrates DETD-AFC and LEVD-AFC, respectively, by fluorometric analysis on a Perkin Elmer Luminescence Spectrometer LS50B (Perkin Elmer; Norwalk, CT) [3]. Hepatocytes were plated at a density of 1.5 × 10 6 in a 60 mm dish and lysed in a 1× lysis buffer (10 mM HEPES, 2 mM EDTA, 0.1% CHAPS, 5 mM DTT, 1 mM PMSF, 10 μg/ml pepstatin A, 10 μg/ml aprotinin, 20 μg/ml leupeptin) by five rapid freeze/thaw cycles.…”

Section: Caspase-3 and Caspase-8 Activitymentioning

confidence: 99%

“…After partial hepatectomy, TGFβ has an integral role in terminating liver regeneration secondary to its hepatocyte anti-proliferative effects. In vitro and in vivo studies have also shown that TGFβ controls hepatocyte growth directly by inducing apoptosis [2][3][4]. Furthermore, TGFβ-induced apoptosis occurs through ROS generation, the mitochondrial permeability transition (MPT), and caspase activation [5].…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen species

et al. 2007

Self Cite

View full text Add to dashboard Cite

TGFβ induces hepatocyte apoptosis via reactive oxygen species (ROS) generation, the mitochondrial permeability transition (MPT), and caspase activation. The role of the Smad pathway in these events is unknown. In this study primary hepatocytes were isolated from Smad3 wild-type (+/+) and knockout (−/−) mice, and were treated with TGFβ (5 ng/ml) and/or trolox (2 mM). ROS generation, MPT, TGFβ-dependent transcription, and apoptosis were assessed in the presence or absence of Smad3 wild-type (WT) and dominant-negative (DN) plasmids. With TGFβ treatment, Smad3 (−/−) hepatocytes did not generate ROS activity, exhibit MPT, activate caspases, or undergo apoptosis when compared to Smad 3 (+/+) hepatocytes. Similarly, transfection of Smad3 (+/+) hepatocytes with DN-Smad3 inhibited TGFβ-mediated transcription, ROS generation, MPT, and apoptosis. However, Smad3 (−/−) cells transfected with WT-Smad3 and treated with TGFβ demonstrated increased transcriptional activity, the MPT, and TGFβ-induced apoptosis. TGFβ-mediated ROS generation occurred through an NADPH-like oxidase pathway since diphenyleneiodonium chloride inhibited ROS induction. In conclusion, TGFβ-induced hepatocyte apoptosis occurs through Smad3 dependent activation of ROS with subsequent activation of the MPT and caspases.

show abstract

Autocrine expression of activated transforming growth factor-β₁ induces apoptosis in normal rat liver

Cited by 37 publications

References 43 publications

Expression of TGF-<i>β</i>1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice

Expression of TGF-<i>β</i>1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice

Molecular mechanism of size control in development and human diseases

Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen species

Contact Info

Product

Resources

About