Microphthalmia-associated transcription factor acts through PEDF to regulate RPE cell migration

Xiaoyin Ma; Li Pan; Xi Jin; Xiaodan Dai; Huirong Li; Bin Wen; Yu Chen; Aobo Ma; Jia Qu; Ling Hou

doi:10.1016/j.yexcr.2011.11.002

Microphthalmia-associated transcription factor acts through PEDF to regulate RPE cell migration

Exp Cell Res. 2012 Feb 1;318(3):251-61. doi: 10.1016/j.yexcr.2011.11.002. Epub 2011 Nov 9.

Authors

Xiaoyin Ma¹, Li Pan, Xi Jin, Xiaodan Dai, Huirong Li, Bin Wen, Yu Chen, Aobo Ma, Jia Qu, Ling Hou

Affiliation

¹ Developmental Cell Biology and Disease Program, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical College, Wenzhou 325003, China.

PMID: 22115973
DOI: 10.1016/j.yexcr.2011.11.002

Abstract

Cells of the retinal pigment epithelium (RPE) play major roles in metabolic functions, maintenance of photoreceptor function, and photoreceptor survival in the retina. They normally form a stable monolayer, but migrate during disease states. Although growth factors produced by the RPE cells primarily control these cellular events, how these factors are regulated in RPE cells remain largely unknown. Here we show that the basic-helix-loop-helix-leucine zipper microphthalmia-associated transcription factor (MITF), which plays central roles in the development and function of a variety of cell types including RPE cells, upregulates the expression of a multifunctional factor PEDF in RPE cells. Consequently, the upregulation of PEDF impairs microtubule assembly and thus inhibits RPE cell migration. Conversely, specific knockdown of PEDF partially rescues the impairment of microtubule assembly and cell migration proceeds in MITF overexpressing stable cells. We conclude that MITF acts through PEDF to inhibit RPE cell migration and to play a significant role in regulating RPE cellular function. We suggest that MITF has a novel and important role in maintaining RPE cells as a stable monolayer and the down-regulation of PEDF that may contribute to retinal degenerative diseases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Movement / drug effects
Cell Movement / genetics*
Cell Movement / physiology
Cells, Cultured
Dose-Response Relationship, Drug
Eye Proteins / antagonists & inhibitors
Eye Proteins / genetics
Eye Proteins / pharmacology
Eye Proteins / physiology*
Gene Expression Regulation / drug effects
Humans
Microphthalmia-Associated Transcription Factor / genetics
Microphthalmia-Associated Transcription Factor / metabolism
Microphthalmia-Associated Transcription Factor / physiology*
Microtubule Proteins / metabolism
Nerve Growth Factors / antagonists & inhibitors
Nerve Growth Factors / genetics
Nerve Growth Factors / pharmacology
Nerve Growth Factors / physiology*
Protein Multimerization / drug effects
Protein Multimerization / genetics
RNA, Small Interfering / pharmacology
Retinal Pigment Epithelium / cytology
Retinal Pigment Epithelium / drug effects
Retinal Pigment Epithelium / metabolism
Retinal Pigment Epithelium / physiology*
Serpins / genetics
Serpins / pharmacology
Serpins / physiology*
Signal Transduction / drug effects
Signal Transduction / genetics
Signal Transduction / physiology
Time Factors
Transfection

Substances

Eye Proteins
Microphthalmia-Associated Transcription Factor
Microtubule Proteins
Nerve Growth Factors
RNA, Small Interfering
Serpins
pigment epithelium-derived factor