Interaction between sphingosine kinase/sphingosine 1 phosphate and transforming growth factor-β/Smads pathways in experimental intestinal fibrosis. An in vivo immunohistochemical study

  • Roberta Sferra | roberta.sferra@univaq.it Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy.
  • Simona Pompili Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Italy.
  • Luca Ventura San Salvatore Hospital, Pathology Division, L’Aquila, Italy.
  • Caroline Dubuquoy Intestinal Biotech Development, Lille, France.
  • Silvia Speca U995-LIRIC-Lille Inflammation Research International Center, University of Lille, France.
  • Eugenio Gaudio Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome, Italy.
  • Giovanni Latella Department of Life, Health and Environmental Sciences, Gastroenterology Unit, University of L’Aquila, Italy.
  • Antonella Vetuschi Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Italy.

Abstract

A concomitant action of multiple profibrotic mediators appears crucial in the development and progression of fibrosis. Sphingosine kinase/sphingosine 1 phosphate and transforming growth factor-β/Smads pathways are both involved in pathogenesis of fibrosis in several organs by controlling differentiation of fibroblasts to myofibroblasts and the epithelial to-mesenchymal transition. However, their direct involvement in chronic colitis-associated fibrosis it is not yet known. In this study we evaluated the immunohistochemical expression of some proteins implicated in sphingosine kinase/sphingosine 1 phosphate and transforming growth factor-β/Smads pathways in Dextrane Sodium Sulphate (DSS)-induced colorectal fibrosis in mice. Compared to control mice, DSS-induced chronic colitis mice developed a marked intestinal fibrosis associated with a concomitant overexpression of TGF-β, p-Smad3, α-SMA, collagen I-III, SPHK1, RhoA, PI3K, Akt, p-Akt, p-mTOR. This study highlights the relationship between the two pathways and the possible role of SPHK1 in the intestinal fibrosis.  These results, if confirmed by in vitro studies, may have important clinical implications in the development of new therapeutical approaches in inflammatory bowel disease.

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Published
2018-07-31
Section
Original Papers
Keywords:
intestinal fibrosis, epithelial to-mesenchymal transition, immunohistochemistry, TGFβ/Smads/, sphingosine 1-phosphate
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How to Cite
Sferra, R., Pompili, S., Ventura, L., Dubuquoy, C., Speca, S., Gaudio, E., Latella, G., & Vetuschi, A. (2018). Interaction between sphingosine kinase/sphingosine 1 phosphate and transforming growth factor-β/Smads pathways in experimental intestinal fibrosis. An in vivo immunohistochemical study. European Journal of Histochemistry, 62(3). https://doi.org/10.4081/ejh.2018.2956