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Open AccessArticle

Topical Application of TGF-β-Activating Peptide, KRFK, Prevents Inflammatory Manifestations in the TSP-1-Deficient Mouse Model of Chronic Ocular Inflammation

1
Ocular Surface Group, IOBA—University of Valladolid, 47011 Valladolid, Spain
2
Department of Ophthalmology, Boston University School of Medicine, Boston, MA 02118, USA
3
Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(1), 9; https://doi.org/10.3390/ijms20010009
Received: 16 November 2018 / Revised: 12 December 2018 / Accepted: 17 December 2018 / Published: 20 December 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Chronic inflammation of the ocular surface poses a risk of vision impairment. The understanding of the molecular mechanisms that are involved in the inflammatory response is critical to identify novel molecular targets. Recently, thrombospondin-1 (TSP-1) has emerged as a key player in ocular surface homeostasis that efficiently activates the TGF-β2 isoform that is predominantly expressed in the ocular mucosa. Here, the potential of the peptide derived from TSP-1 (KRFK), that can activate TGF-β, is proposed as a potentially applicable therapeutic for chronic ocular surface inflammatory disorders. Our in vitro results confirm that the chosen peptide activates TGF-β, reducing the expression of co-stimulatory molecules on dendritic cells, driving them towards a tolerogenic phenotype. For the in vivo studies, the TSP-1−/− mouse is used as a pre-clinical model of chronic ocular inflammation. We observe that the topical application of KRFK alters the peripheral balance of effectors by reducing the proportion of pathogenic Th1 and Th17 cells while increasing Treg cell proportion in cervical lymph nodes. In line with these findings, the development of chronic ocular surface inflammation is significantly prevented in KRFK-treated TSP-1−/− mice, as assessed by clinical parameters and inflammatory cytokine expression in conjunctival and lacrimal gland tissues. Together, our results identify the KRFK peptide as a novel therapeutic option to prevent the development of chronic inflammatory manifestations of the ocular surface. View Full-Text
Keywords: Inflammation; KRFK peptide; ocular surface; thrombospondin-1; transforming growth factor-β Inflammation; KRFK peptide; ocular surface; thrombospondin-1; transforming growth factor-β
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MDPI and ACS Style

Soriano-Romaní, L.; Contreras-Ruiz, L.; López-García, A.; Diebold, Y.; Masli, S. Topical Application of TGF-β-Activating Peptide, KRFK, Prevents Inflammatory Manifestations in the TSP-1-Deficient Mouse Model of Chronic Ocular Inflammation. Int. J. Mol. Sci. 2019, 20, 9. https://doi.org/10.3390/ijms20010009

AMA Style

Soriano-Romaní L, Contreras-Ruiz L, López-García A, Diebold Y, Masli S. Topical Application of TGF-β-Activating Peptide, KRFK, Prevents Inflammatory Manifestations in the TSP-1-Deficient Mouse Model of Chronic Ocular Inflammation. International Journal of Molecular Sciences. 2019; 20(1):9. https://doi.org/10.3390/ijms20010009

Chicago/Turabian Style

Soriano-Romaní, Laura; Contreras-Ruiz, Laura; López-García, Antonio; Diebold, Yolanda; Masli, Sharmila. 2019. "Topical Application of TGF-β-Activating Peptide, KRFK, Prevents Inflammatory Manifestations in the TSP-1-Deficient Mouse Model of Chronic Ocular Inflammation" Int. J. Mol. Sci. 20, no. 1: 9. https://doi.org/10.3390/ijms20010009

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