Unexpected news in renal fibrosis

Oliver, Juan A.

doi:10.1172/jci17399

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…Because radiation causes tumor cells to express pro-angiogenic factors ( 25 ) and is clinically known to cause fibrosis, we asked if radiation might also induce profibrotic factors and which cells other than macrophages ( 26 – 28 ) might contribute to radiation-induced fibrosis. To this end, we used a coculture model of human fibroblasts in conjunction with either human endothelial cells (human umbilical vein endothelial cells [HUVECs] and human lung microvascular endothelial cells [HLMVECs]) or a human lung cancer cell line (A549).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis

Abdollahi

Gong

et al. 2005

The Journal of Experimental Medicine

338

274

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Pulmonary fibrosis is the consequence of a variety of diseases with no satisfying treatment option. Therapy-induced fibrosis also limits the efficacy of chemotherapy and radiotherapy in numerous cancers. Here, we studied the potential of platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitors (RTKIs) to attenuate radiation-induced pulmonary fibrosis. Thoraces of C57BL/6 mice were irradiated (20 Gy), and mice were treated with three distinct PDGF RTKIs (SU9518, SU11657, or Imatinib). Irradiation was found to induce severe lung fibrosis resulting in dramatically reduced mouse survival. Treatment with PDGF RTKIs markedly attenuated the development of pulmonary fibrosis in excellent correlation with clinical, histological, and computed tomography results. Importantly, RTKIs also prolonged the life span of irradiated mice. We found that radiation up-regulated expression of PDGF (A–D) isoforms leading to phosphorylation of PDGF receptor, which was strongly inhibited by RTKIs. Our findings suggest a pivotal role of PDGF signaling in the pathogenesis of pulmonary fibrosis and indicate that inhibition of fibrogenesis, rather than inflammation, is critical to antifibrotic treatment. This study points the way to a potential new approach for treating idiopathic or therapy-related forms of lung fibrosis.

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Section: Resultsmentioning

confidence: 99%

Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis

Abdollahi

Gong

et al. 2005

The Journal of Experimental Medicine

338

274

View full text Add to dashboard Cite

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“…The presence and activation of alveolar macrophages are also likely to influence tissue remodeling and fibrogenesis. Although macrophages have long been considered an initiator of the fibrotic process in UIP/IPF (126,127), recent evidence suggests that under certain conditions they may also mediate antifibrotic effects (128,129).…”

Section: Inflammatory Cells: Modulators Of Fibrosismentioning

confidence: 99%

Mechanisms of Pulmonary Fibrosis

et al. 2004

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Tissue injury evokes highly conserved, tightly regulated inflammatory responses and less well-understood host repair responses. Both inflammation and repair involve the recruitment, activation, apoptosis, and eventual clearance of key effector cells. In this review, we propose the concept of pulmonary fibrosis as a dysregulated repair process that is perpetually "turned on" even though classical inflammatory pathways may be dampened or "switched off." Significant regional heterogeneity, with varied histopathological patterns of inflammation and fibrosis, has been observed in individual patients with idiopathic pulmonary fibrosis. We discuss environmental factors and host response factors, such as genetic susceptibility and age, that may influence these varied manifestations. Better understanding of the mechanisms of lung repair, which include alveolar reepithelialization, myofibroblast differentiation/activation, and apoptosis, should offer more effective therapeutic options for progressive pulmonary fibrosis.

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“…The increased apoptotic environment and abnormal extracellular matrix are detrimental to epithelial cell survival, leading to atrophy. Thus chronic renal atrophy and interstitial fibrosis are directly associated with one another (94), and activation of apoptotic pathways contributes to the extensive cell loss characteristic of progressive tubulointerstitial diseases.…”

Section: Pgi 2 and Cell Fatementioning

confidence: 99%

Prostacyclin signaling in the kidney: implications for health and disease

Nasrallah

Hébert

2005

American Journal of Physiology-Renal Physiology

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The balance between vasodilator and vasoconstrictor pathways is key to the maintenance of homeostasis and the outcome of disease. In the kidney, prostaglandins (PGs) uphold this balance and regulate renal function: hemodynamics, renin secretion, growth responses, tubular transport processes, and cell fate. With the advent of cyclooxygenase (COX)-2-selective inhibitors, targeted deletions in mice (COX knockouts, PG receptor knockouts), and the discovery of intracrine signaling options for PGs (peroxisome proliferator-activated receptors and perinuclear PGE(2) receptors: EP(1,3,4)), many advances have been made in the study of arachidonic acid metabolites. Although prostacyclin (PGI(2)) is a major product of the COX pathway, there is very little emphasis on its importance to the kidney. This review will discuss PGI(2) biology and its relevance to different aspects of renal disease (growth, fibrosis, apoptosis), highlighting the most significant research from the past decade of PGI(2) literature, what we have learned from other organ systems, while stressing the significance of cross talk between various PGI(2) signaling pathways and its implications for renal health and disease.

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Unexpected news in renal fibrosis

Cited by 5 publications

References 27 publications

Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis

Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis

Mechanisms of Pulmonary Fibrosis

Prostacyclin signaling in the kidney: implications for health and disease

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