title: Microphthalmia-associated transcription factor acts through PEDF to regulate RPE cell migration.
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.
authors: Developmental Cell Biology and Disease Program, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical College, Wenzhou 325003, China.
authors: Xiaoyin
authors: X
authors: Ma
authors: Li
authors: L
authors: Pan
authors: Xi
authors: X
authors: Jin
authors: Xiaodan
authors: X
authors: Dai
authors: Huirong
authors: H
authors: Li
authors: Bin
authors: B
authors: Wen
authors: Yu
authors: Y
authors: Chen
authors: Aobo
authors: A
authors: Ma
authors: Jia
authors: J
authors: Qu
authors: Ling
authors: L
authors: Hou
mesh_terms: D002465:Cell Movement / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008868:Microtubule Proteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D055503:Protein Multimerization / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015843:Serpins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014162:Transfection; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D051739:Microphthalmia-Associated Transcription Factor; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; D034741:RNA, Small Interfering; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor