PMID:23539510

Citation	'Hampel, U, Klonisch, T, Sel, S, Schulze, U and Paulsen, FP (2013) Insulin-like Factor 3 promotes wound healing at the ocular surface. Endocrinology '
Abstract	Tear fluid is known to contain many different hormones with relevance for ocular surface homeostasis. We studied the presence and functional role of insulin-like factor 3 (INSL3) and its cognate receptor RXFP2 at the ocular surface and in tears. Expression of human INSL3 and RXFP2 was determined in tissues of the ocular surface, lacrimal apparatus, in human corneal (HCE), conjunctival (HCjE), sebaceous (SC) epithelial cell lines and in human tears by RT-PCR and ELISA. We investigated effects of human recombinant (hr)INSL3 on cell proliferation and cell migration and the influence of hrINSL3 on the expression of MMP2, -9, -13 and TIMP1 and -2 was quantified by real-time PCR and ELISA in HCE, HCjE and SC cells. We used a C57BL/6 mouse corneal defect model to elucidate the effect of topical application of hrINSL3 on corneal wound healing. INSL3 and RXFP2 transcripts and INSL3 protein were detected in all tissues and cell lines investigated. Significantly higher concentrations of INSL3 were detected in tears from male vs. female volunteers. Stimulation of HCE, HCjE and SC with hrINSL3 significantly increased cell proliferation in HCjE and SC and migration of HCjE. Treatment with hrINSL3 for 24 h regulated MMP2, TIMP1 and TIMP2 expression. The local application of hrINSL3 onto denuded corneal surface resulted in significantly accelerated corneal wound healing in mice. These findings suggest a novel and gender specific role for INSL3 and cognate receptor RXFP2 signaling in ocular surface homeostasis and determined a novel role for hrINSL3 in corneal wound healing.
Links	PubMed Online version:10.1210/en.2012-2201
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:INSL3		GO:0090303: positive regulation of wound healing	ECO:0000314:		P		Figure 5. Shows accelerated corneal wound healing after alkali burning. Higher concentrations of INSL3 correlate with quicker healing.	complete CACAO 7404
HUMAN:INSL3		GO:0010634: positive regulation of epithelial cell migration	ECO:0000314:		P		Figure 3. Shows significant higher scratch closure rate of corneal an conjuctival epithelial cells. Under the effects of migration inhibitors scratch closure could not be induced. Under the effects of cell proliferation inhibitors scratch closure was unaffected.	complete CACAO 7401
HUMAN:INSL3	involved_in	GO:0010634: positive regulation of epithelial cell migration	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:INSL3	involved_in	GO:0090303: positive regulation of wound healing	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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