Lumican is required for neutrophil extravasation following corneal injury and wound healing

Abstract

SummaryAn important aspect of wound healing is the recruitment of neutrophils to the site of infection or tissue injury. Lumican, an extracellular matrix component belonging to the small leucine rich proteoglycan (SLRP) family, is one of the major keratan sulfate proteoglycans (KSPGs) within the corneal stroma. Increasing evidence indicates that lumican can serve as a regulatory molecule for several cellular processes, including cell proliferation and migration. In the present study, we addressed the role of lumican in the process of extravasation of polymorphonuclear leukocytes (PMNs) during the early inflammatory phase present in the healing of the corneal epithelium following debridement. We used Lum -/-mice and a novel transgenic mouse, Lum -/-,Kera-Lum, which expresses lumican only in the corneal stroma, to assess the role of lumican in PMN extravasation into injured corneas. Our results showed that PMNs did not readily invade injured corneas of Lum -/-mice and this defect was rescued by the expression of lumican in the corneas of Lum -/-,Kera-Lum mice. The presence of lumican in situ facilitates PMN infiltration into the peritoneal cavity in casein-induced inflammation. Our findings are consistent with the notion that in addition to regulating the collagen fibril architecture, lumican acts to aid neutrophil recruitment and invasion following corneal damage and inflammation.

Lumican Regulates Ventilation-Induced Epithelial-Mesenchymal Transition Through Extracelluar Signal-Regulated Kinase Pathway

“…29 In addition to regulating the collagen fi bril architecture within the ECM of lung, previous studies of mice demonstrated that lack of lumican reduced neutrophil infi ltration into damaged tissue because of the absence of chemokine gradient and a scaffold for neutrophil extravasation. 30,31 We found that mechanical ventilation downregulated expression of epithelial marker E-cadherin but upregulated expression of mesenchymal markers S100A4/fi broblastspecifi c protein-1 and a -SMA. Using lumican-defi cient mice, we observed a decrease of MIP-2 and TGF-b 1 production and expression of TGF-b 1 -inducible EMT markers, suggesting the involvement of lumican in the regulation of fi brogenesis of VILI.…”

TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

“…Lumican is vital for the correct formation of collagen fibrils and promotes cell adhesion and migration (40,(45)(46)(47). Lumican knockout mice have multiple defects, including corneal opacity, skin and tendon fragility, and defective leukocyte migration (46,(48)(49)(50)(51).…”

Quantitative Assessment of Ultrastructure and Light Scatter in Mouse Corneal Debridement Wounds

“…In recent years the availability of mutant and genetic knockout mice has provided researchers with the opportunity to selectively investigate the role that specific molecules play in corneal injury repair, and this has led to a burgeoning of interest in the mouse as a model for corneal wound healing. [12][13][14][15][16] Much of the focus of previous studies of murine wound healing has been on the acute phase of healing. We understand little as to the long-term consequences of wounding in terms of disruption of the stromal ECM and how this affects light scatter.…”