Literature DB >> 23950153

Inhibition of miR-205 impairs the wound-healing process in human corneal epithelial cells by targeting KIR4.1 (KCNJ10).

Daohong Lin1, Adna Halilovic, Peng Yue, Lars Bellner, Kemeng Wang, Lijun Wang, Chengbiao Zhang.   

Abstract

PURPOSE: The aim of the study was to test the hypotheses that injury stimulates the expression of miR-205, which in turn inhibits KCNJ10 channels by targeting its 3' UTR, thereby facilitating the wound-healing process in human corneal epithelial cells (HCECs).
METHODS: A stem-loop qRT-PCR was used to examine the miR-205 expression. BrdU cell proliferation assay and wound scratch assay were applied to measure the effect of miR-205 mimic or antagomer in HCECs. The patch-clamp technique, dual luciferase reporter assay, and Western blot analysis were employed to test whether miR-205 regulates KCNJ10, one of the target genes of miR-205. Both of the primary human and mouse corneal epithelial cells (pH/MCECs) were employed to further confirm the observations obtained in HCECs.
RESULTS: The scratch injury in pH/MCECs increased the expression of miR-205 and decreased the expression of KCNJ10 within 24 hours. The notion that miR-205 may target KCNJ10 was supported by dual luciferase reporter assay showing an inhibition effect of miR-205 on 3' UTR of KCNJ10. Application of miR-205 antagomer significantly delayed the regrowth in wounded HCECs. However, inhibition of KCNJ10 partially abolished the effect from miR-205 antagomer and restored the healing process. Moreover, overexpression miR-205 antagomer enhanced the protein expression of KCNJ10 but not KCNJ16. In addition, patch-clamp demonstrated that inhibition of endogenous miR-205 expression increased Ba²⁺-sensitive inwardly rectifying K⁺ channels. In addition, an electrophysiological study of pHCECs showed the presence of KCNJ10-like 20 pS K⁺ channels and scratch injury significantly decreased the Ba²⁺-sensitive inwardly rectifying K⁺ currents.
CONCLUSIONS: miR-205 stimulates wound healing by inhibiting its target gene KCNJ10.

Entities:  

Keywords:  KCNJ10; miR-205; wound healing

Mesh:

Substances:

Year:  2013        PMID: 23950153     DOI: 10.1167/iovs.12-11577

Source DB:  PubMed          Journal:  Invest Ophthalmol Vis Sci        ISSN: 0146-0404            Impact factor:   4.799


  21 in total

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