Moesin as a key cytoskeleton regulator in corneal fibrosis.

Abstract

PURPOSE:

: Corneal fibrosis is the third leading cause of blindness worldwide. α-Smooth muscle actin (SMA), a marker of fibrosis, is closely regulated through an intermediate group of submembrane molecules - cytoskeleton regulators. The purpose of this study was to elucidate the role of specific cytoskeleton regulators in a mouse model of corneal fibrosis.

METHODS:

: A mouse model of corneal fibrosis was developed using anterior keratectomy (AK) and the topical application of transforming growth factor (TGF)-β1 (1 μg/ml). The RT² Profiler™ PCR Array for cytoskeleton regulators was used to assay changes in levels of specific members of this class of proteins. Moesin siRNA was delivered into the corneal stroma by iontophoresis in vivo. Transformation of the corneal keratocyte-to-myofibroblast in corneal fibrosis, as defined by the expression of α-SMA, was determined by Western blot.

RESULTS:

: After AK and topical application of TGF-β1, moesin was the most highly upregulated gene among 84 cytoskeleton regulator genes; iontophoresing moesin siRNA into the corneal stroma reduced the expression of α-SMA to 0.22-, 0.52-, and 0.31-fold of control at postoperative (PO) day 1, 3, and 5, respectively; also, upregulation of phospho-Smad 2 induced by TGF-β1 was reduced by moesin siRNA to 0.59-, 0.56-, and 0.31-fold of control and expression of phospho-Smad 3 was reduced to 0.58-, 0.53-, and 0.47-fold of control at the same PO days.

CONCLUSIONS:

: Moesin may be a potential drug target for inhibiting corneal fibrosis, and the details of moesin-related signaling pathways would be critical for understanding corneal fibrosis.

• Authors: Hong-Yuan Zhu, Sia-Wey Yeo, Jennifer Ng, Hla Myint Htoon, R W Beuerman
• Journal: The ocular surface (Ocul Surf) Vol. 11 Issue 2 Pg. 119-32 (Apr 2013) ISSN: 1542-0124 [Print] United States
• PMID: 23583046 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Microfilament Proteins
• moesin
• RNA

Topics

• Animals
• Cornea (metabolism, pathology)
• Corneal Diseases (genetics, metabolism, pathology)
• Cytoskeleton (genetics, metabolism)
• Disease Models, Animal
• Fibrosis (genetics, metabolism, pathology)
• Gene Expression Regulation
• Mice
• Mice, Inbred C57BL
• Microfilament Proteins (biosynthesis, genetics)
• Polymerase Chain Reaction
• RNA (genetics)