Abnormal Mucosal Extracellular Matrix Deposition Is Associated with Increased TGF-β Receptor-expressing Mesenchymal Cells in a Mouse Model of Colitis

Whiting, Christine V.; Tarlton, John F; Bailey, Michael; Morgan, Clare; Bland, Paul W.

doi:10.1177/002215540305100908

Cited by 18 publications

(23 citation statements)

References 56 publications

(79 reference statements)

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“…A much smaller (3.1%) proportion were LacZ-positive in cells isolated from saline-treated animals, probably due to basal contribution of endothelial-derived fibroblasts under physiological condition. The finding that both SLFs and BLFs were negative for CD31 in our fibroblasts culture system might be supported by the previous study (33) and also explained by the manufacturer's recommendations that many kinds of growth factors are usually needed to keep primary cultured endothelial cells in vitro (34). Recent lineage tracking analysis in combination with a Tie2-driven Cre/loxP reporter system suggested that only 1-5% of the endothelium in liver may be derived from BM-derived EPC (35).…”

Section: Discussionsupporting

confidence: 83%

Endothelial–Mesenchymal Transition in Bleomycin-Induced Pulmonary Fibrosis

Hashimoto¹,

Phan²,

Imaizumi³

et al. 2010

Am J Respir Cell Mol Biol

360

310

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The pathological hallmark lesions in idiopathic pulmonary fibrosis are the fibroblastic foci, in which fibroblasts are thought to be involved in the tissue remodeling, matrix deposition, and cross-talk with alveolar epithelium. Recent evidence indicates that some fibroblasts in fibrosis may be derived from bone marrow progenitors as well as from epithelial cells through epithelial-mesenchymal transition. To evaluate whether endothelial cells could represent an additional source for fibroblasts, bleomycin-induced lung fibrosis was established in Tie2-Cre/CAG-CAT-LacZ double-transgenic mice, in which LacZ was stably expressed in pan-endothelial cells. Combined X-gal staining and immunocytochemical staining for type I collagen and a-smooth muscle actin revealed the presence of X-galpositive cells in lung fibroblast cultures from bleomycin-treated mice. To explore the underlying mechanisms, by which loss of endothelial-specific markers and gain of mesenchymal phenotypes could be involved in microvascular endothelial cells, the effects of activated Ras and TGF-b on the microvascular endothelial cell line MS1 were analyzed. Combined treatment with activated Ras and TGF-b caused a significant loss of endothelial-specific markers, while inducing de novo mesenchymal phenotypes. The altered expression of these markers in MS1 cells with activated Ras persisted after withdrawal of TGF-b in vitro and in vivo. These findings are the first to show that lung capillary endothelial cells could give rise to significant numbers of fibroblasts through an endothelial-mesenchymal transition in bleomycin-induced lung fibrosis model.

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Section: Discussionsupporting

confidence: 83%

Endothelial–Mesenchymal Transition in Bleomycin-Induced Pulmonary Fibrosis

Hashimoto¹,

Phan²,

Imaizumi³

et al. 2010

Am J Respir Cell Mol Biol

360

310

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“…TGFβ1 receptor signaling has been shown to play an essential role during the pathogenesis and recovery of inflammation-related colitis [3,4,5,6,7], but through unclear mechanism. Also, MSCs transplantation has been reported to promote the recovery from DSS-induced colitis [9,10,11,12], whereas the underlying molecular mechanisms remain largely undefined.…”

Section: Discussionmentioning

confidence: 99%

“…Transforming growth factor β (TGFβ) receptor signaling has a well-established role in regulating the progression and recovery of inflammation-related colitis [3,4,5,6,7,8]. However, the precise mechanisms have not been completely clarified.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Recruit Macrophages to Alleviate Experimental Colitis Through TGFβ1

Liu

Zhang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate dextran sulfate sodium (DSS) -induced colitis through modulation of transforming growth factor β (TGFβ) receptor signaling. However, the exact molecular mechanisms are not known. Methods: Here, we transplanted primary mouse MSCs or injected TGFβ1 into mice with DSS-induced colitis. Cells were purified by flow cytometry. Gene expression was analyzed by RT-qPCR. Results: We found that MSCs significantly alleviated the DSS-induced colitis, and the major sources for TGFβ1 were macrophages that were recruited by MSCs. Specific ablation of macrophages completely abolished the anti-inflammatory effects of MSCs. On the other hand, TGFβ1 administration, without the presence of MSCs, was sufficient to reduce the severity of DSS-induced colitis. Conclusions: Taken together, our data suggest that MSCs transplantation may recruit macrophages to produce TGFβ1, which mitigates the pathology of colitis. Thus, MSCs transplantation appears to be a promising therapy for severe enteritis.

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“…g Masur et al (1996). h Estimated as median value from microphotographies obtained by Whiting et al (2003). i Median value between data reported by Egidy et al (2000) and Whiting et al (2003).…”

Section: Cellular Relative Abundancesmentioning

confidence: 99%