Initiation of fibrosis in the integrin Αvβ6 knockout mice. (March 2019)

• Record Type: Journal Article
• Authors: Wu, Wenjing; Hutcheon, Audrey E.K.; Sriram, Sriniwas; Tran, Jennifer A.; Zieske, James D.
• Is Part Of: Experimental eye research. Volume 180(2019)
• Page Start: 23
• Page End: 28
• Publication Date: 2019-03
• Subjects: Fibrosis -- Wound healing -- α-smooth muscle actin -- Thrombospondin-1 -- Integrin αVβ6; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2018.11.027
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: We previously demonstrated that β6 knockout mice showed impaired wound repair in corneal debridement and keratectomy wounds. In the current investigation, we continued our examination of integrin αvβ6 in order to determine if it was required for the initiation of wound healing in a corneal wound model that normally heals in a fibrotic manner. A full-thickness corneal incision was made in C57BL/6 J wild type (WT) and C57BL/6-Itgb6 KO (β6 −/− ) mice. The mice were observed at 3, 7, 14, and 28 days post-incision. The morphology of corneal restoration was observed in tissue sections stained with hemotoxilin and eosin (H&E). In addition, indirect-immunofluorescence (IF) was performed on sections and/or whole mounts to evaluate the immunolocalization of α-smooth muscle actin (SMA) and thrombospondin-1 (TSP-1). H&E staining revealed that the corneas in β6 −/− mice healed slower than those in WT mice, with an obvious delay in the restoration of the stromal matrix and epithelium. In sections at 3 and 7 days, SMA and TSP-1 were greatly reduced in the β6 −/− mice as compared to WT, but peaked at 28 days after incision. Whole mount SMA IF results were consistent with those from sections. Therefore, the initiation of fibrosis was inhibited by the lack of αvβ6; however, there appeared to be an alternate mechanism that initiated fibrosis 7–14 days later. Localization of TSP-1 correlated with expression of SMA whether wound healing was delayed or initiated immediately after wounding. Highlights: β6 −/− mouse corneas healed slower than WT mice. SMA and TSP-1 was greatly reduced in β6 −/− mouse corneas at early time points. At later time points SMA and TSP-1 increased and peaked 28 days post-incision. The initiation of fibrosis was inhibited by the lack of αvβ6. An alternate mechanism in β6 −/− mice initiated fibrosis 7–14 days later than in WT.