IL-13 Signaling via IL-13Rα2 Induces Major Downstream Fibrogenic Factors Mediating Fibrosis in Chronic TNBS Colitis

Fichtner‐Feigl, Stefan; Young, Cheryl; Kitani, Atsushi; Geissler, Edward K.; Schlitt, Hans-Jürgen; Strober, Warren

doi:10.1053/j.gastro.2008.08.055

Cited by 145 publications

(124 citation statements)

References 29 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…Gut fibrosis in a mouse model of Crohn's disease was similarly linked to IL-13-induced fibrotic responses mediated through cellular Egr-1. 44 Together, these results highlight the importance of Egr-1 as a critical intracellular mediator of fibrotic responses involving TGF-ß or IL-13. In contrast, lung fibrosis induced by transgenic TGF-␣ appeared to be exacerbated, rather than prevented, in mice lacking Egr-1.…”

Section: Discussionmentioning

confidence: 74%

Essential Roles for Early Growth Response Transcription Factor Egr-1 in Tissue Fibrosis and Wound Healing

Melichian

Garza

et al. 2009

The American Journal of Pathology

100

View full text Add to dashboard Cite

The early growth response gene (Egr-1) codes for a zinc finger transcription factor that has important roles in the regulation of cell growth, differentiation, and survival. Aberrant Egr-1 expression is implicated in carcinogenesis, inflammation, atherosclerosis, and ischemic injury. We reported previously that normal fibroblasts stimulated by transforming growth factor-ß showed rapid and transient induction of Egr-1. Moreover, we observed that tissue expression of Egr-1 was elevated in patients with scleroderma, which suggests that Egr-1 may be involved in tissue repair and fibrosis. Here, we investigated matrix remodeling and wound healing in mice harboring gain of function or loss of function mutations of Egr-1. Using the model of bleomycin-induced scleroderma, we found that the early influx of inflammatory cells into the skin and lungs, and the subsequent development of fibrosis in these organs, were markedly attenuated in Egr-1 null mice. Furthermore, full-thickness incisional skin wound healing was impaired, and skin fibroblasts lacking Egr-1 showed reduced migration and myofibroblast transdifferentiation in vitro. In contrast, transgenic mice with fibroblast-specific Egr-1 overexpression showed exuberant tissue repair, with enhanced collagen accumulation and increased tensile strength of incisional wounds. Together, these results point to the fundamental role that Egr-1 plays in the regulation of transforming growth factor-ß-dependent physiological and pathological matrix

show abstract

Section: Discussionmentioning

confidence: 74%

Essential Roles for Early Growth Response Transcription Factor Egr-1 in Tissue Fibrosis and Wound Healing

Melichian

Garza

et al. 2009

The American Journal of Pathology

100

View full text Add to dashboard Cite

show abstract

“…Treatment of mice with bleomycin promotes IL-13-dependent pulmonary fibrosis (19), and inhibition of IL-13 activity ameliorates fibrosis associated with chronic trinitrobenzene sulfonic acid-induced colitis (47). Notably, pulmonary overexpression of IL-13 in the lung was sufficient to induce pulmonary fibrosis (48).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-13 (IL-13)/IL-13 Receptor α1 (IL-13Rα1) Signaling Regulates Intestinal Epithelial Cystic Fibrosis Transmembrane Conductance Regulator Channel-dependent Cl− Secretion

Wu¹,

Ahrens²,

Osterfeld³

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Interleukin-13 (IL-13) has been linked to the pathogenesis of inflammatory diseases of the gastrointestinal tract. It is postulated that IL-13 drives inflammatory lesions through the modulation of both hematopoietic and nonhematopoietic cell function in the intestine. To delineate the relevant contribution of elevated levels of intestinal IL-13 to intestinal structure and function, we generated an intestinal IL-13 transgenic mouse (iIL-13Tg). We show that constitutive overexpression of IL-13 in the small bowel induces modification of intestinal epithelial architecture (villus blunting, goblet cell hyperplasia, and increased epithelial proliferation) and epithelial function (altered basolateral 3 apical Cl ؊ ion conductance). Pharmacological analyses in vitro and in vivo determined that elevated Cl

show abstract

“…To achieve IL-13 blockade, we administered a plasmid-encoding soluble IL-13 receptor-α2-Fc fusion protein (pCI-sIL-13Rα 2 -Fc) or a control plasmid (pCI empty vector) by intranasal instillation every other day, starting on day 20 after initiation of chronic oxa-colitis (28,29). We verified that such intranasal administration of the sIL-13Rα 2 -Fc plasmid results in expression of sIL-13Rα 2 -Fc in colonic tissue by demonstrating that human Ig-Fc (a component of the plasmid product) is expressed in colonic tissue extracts after administration of the plasmid (data not shown).…”

Section: Nkt Cells Producing Il-13 Drive Chronic Oxa-colitis Previoumentioning

confidence: 99%

Tumor development in murine ulcerative colitis depends on MyD88 signaling of colonic F4/80+CD11bhighGr1low macrophages

Schiechl¹,

Bauer²,

Fuss³

et al. 2011

J. Clin. Invest.

Self Cite

View full text Add to dashboard Cite

IL-13 Signaling via IL-13Rα2 Induces Major Downstream Fibrogenic Factors Mediating Fibrosis in Chronic TNBS Colitis

Cited by 145 publications

References 29 publications

Essential Roles for Early Growth Response Transcription Factor Egr-1 in Tissue Fibrosis and Wound Healing

Essential Roles for Early Growth Response Transcription Factor Egr-1 in Tissue Fibrosis and Wound Healing

Interleukin-13 (IL-13)/IL-13 Receptor α1 (IL-13Rα1) Signaling Regulates Intestinal Epithelial Cystic Fibrosis Transmembrane Conductance Regulator Channel-dependent Cl− Secretion

Tumor development in murine ulcerative colitis depends on MyD88 signaling of colonic F4/80+CD11bhighGr1low macrophages

Contact Info

Product

Resources

About