The Effects of Aerosolized STAT1 Antisense Oligodeoxynucleotides on Rat Pulmonary Fibrosis

Wang, Wen Jun; Liu, Bin; Zeng, Ming; Zhu, Changqing; Fan, Xian

doi:10.1038/cmi.2009.7

Cited by 16 publications

(9 citation statements)

References 25 publications

(30 reference statements)

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“…Studies in mouse models of bleomycin-induced lung fibrosis and CCl4-induced liver fibrosis suggested a protective role for STAT1 [102,103]. Another study in rats suggested that STAT1 inhibits bleomycin-induced lung fibrosis [104], while reduced SOCS1 expression has been linked to pulmonary fibrosis in patients and in animal models [105]. JANEX, a specific JAK3 inhibitor, prevented the development of autoimmune type 1 diabetes in NOD mice by modulating T cell cytokine profile [106].…”

Section: Putative Signaling Mediating Diabetes-induced Microvasculmentioning

confidence: 99%

“…Furthermore, JAK3 −/− mice are protected from streptozotocin-induced diabetes and IL-1β and IFN-γ-induced islet damage [107]. These data suggest that STAT activation plays a significant role in pancreatic iNOS induction and the ensuing systemic inflammation in DM as well as in the fibrogenesis process [101,102,103,104,105]. Therefore, lung-targeted modulation of this pathway, could also prevent DM-induced pulmonary fibrosis by decreasing DM-induced platelet activation and lung inflammation.…”

Section: Putative Signaling Mediating Diabetes-induced Microvasculmentioning

confidence: 99%

See 1 more Smart Citation

Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation

Jagadapillai

Rane

Lin

et al. 2016

IJMS

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Diabetes is strongly associated with systemic inflammation and oxidative stress, but its effect on pulmonary vascular disease and lung function has often been disregarded. Several studies identified restrictive lung disease and fibrotic changes in diabetic patients and in animal models of diabetes. While microvascular dysfunction is a well-known complication of diabetes, the mechanisms leading to diabetes-induced lung injury have largely been disregarded. We described the potential involvement of diabetes-induced platelet-endothelial interactions in perpetuating vascular inflammation and oxidative injury leading to fibrotic changes in the lung. Changes in nitric oxide synthase (NOS) activation and decreased NO bioavailability in the diabetic lung increase platelet activation and vascular injury and may account for platelet hyperreactivity reported in diabetic patients. Additionally, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway has been reported to mediate pancreatic islet damage, and is implicated in the onset of diabetes, inflammation and vascular injury. Many growth factors and diabetes-induced agonists act via the JAK/STAT pathway. Other studies reported the contribution of the JAK/STAT pathway to the regulation of the pulmonary fibrotic process but the role of this pathway in the development of diabetic lung fibrosis has not been considered. These observations may open new therapeutic perspectives for modulating multiple pathways to mitigate diabetes onset or its pulmonary consequences.

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Section: Putative Signaling Mediating Diabetes-induced Microvasculmentioning

confidence: 99%

Section: Putative Signaling Mediating Diabetes-induced Microvasculmentioning

confidence: 99%

Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation

Jagadapillai

Rane

Lin

et al. 2016

IJMS

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“…STAT proteins regulate cell survival and apoptosis (15), and accordingly there has been much recent interest in the role of STAT1/3 in fibrosis. Studies in mouse models of bleomycin (BLM)-induced lung fibrosis and carbon tetrachloride (CCl 4 )-induced liver fibrosis have suggested a protective role (16,17), whereas a recent study in rats suggests that STAT1 inhibits BLM-induced lung fibrosis, as measured by reduced collagen levels (18). Studies in mouse models of bleomycin (BLM)-induced lung fibrosis and carbon tetrachloride (CCl 4 )-induced liver fibrosis have suggested a protective role (16,17), whereas a recent study in rats suggests that STAT1 inhibits BLM-induced lung fibrosis, as measured by reduced collagen levels (18).…”

Section: Stat Activation and Fibrosismentioning

confidence: 99%

Stat3

Prêle¹,

Yao²,

O’Donoghue³

et al. 2012

Proc Am Thorac Soc

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“…Walters et al demonstrated that STAT1 deficient (STAT1 / ) mice exhibited more severe pulmonary fibrosis after bleomycin injury compared to wild type (STAT1 +/+ ) mice and that fibroblast proliferation stimulated by growth factors (EGF, PDGF) was enhanced in STAT1 deficient mice [56]. Furthermore, treatment with STAT1 antisense ameliorates alveolitis and fibrosis, inhibits the expressions of inflammatory mediators, decreases the content of hydroxyproline, and suppresses the expressions of type I and type III collagen mRNA in BLM-induced rat pulmonary fibrosis [64]. Thus, it appears that STAT1 plays an anti-fibrotic effect in the lung.…”

Section: Roles Of Other Stat Isoforms (Stat1 Stat5 and Stat6) In Tismentioning

confidence: 90%

The Role of STAT 3 in Tissue Fibrosis

Li¹,

Zhuang²

2011

curr chem biol

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Signal transducer and activator of transcription 3 (STAT3) is a transcriptional factor and has been implicated in cell proliferation, survival and differentiation. Recent studies demonstrate that STAT3 activity is persistently elevated in patients with some chronic disorders, and required for the development and progression of fibrosis in a variety of tissues including kidney, bone marrow and skin. On the other hand, STAT3 is implicated in tissue protection against fibrosis in the heart following acute injury. Moreover, STAT3 can either promote or protect against tissue fibrosis in chronic liver disease models, depending on etiologies. The underlying mechanisms by which STAT3 mediates those cellular events are not fully understood, but the profibrotic action of STAT3 is mostly associated with activation and proliferation of fibroblasts, deposition of excessive extracellular matrix proteins, and overproduction of some cytokines. In this review article, we discuss the role of STAT3 in tissue fibrosis and the effect of the STAT3 pathway inhibition on the proliferation and activation of fibroblasts in vitro and fibrogenesis in various animal models.

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The Effects of Aerosolized STAT1 Antisense Oligodeoxynucleotides on Rat Pulmonary Fibrosis

Cited by 16 publications

References 25 publications

Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation

Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation

Stat3

The Role of STAT 3 in Tissue Fibrosis

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