Epithelial-mesenchymal transition as a therapeutic target for prevention of ocular tissue fibrosis.
Fibrotic diseases are characterized by the appearance of myofibroblasts, the key cell type involved in the fibrogenic reaction, and by excess accumulation of extracellular matrix with resultant tissue contraction and impaired function. Myofiborblasts are generated by fibroblast-myofibrobalst conversion, and in certain tissues through epithelial-mesenchymal transition (EMT), a process through which an epithelial cell changes its phenotype to become more like a mesenchymal cell. Although inflammatory/fibrogenic growth factors/cytokines produced by injured tissues orchestrate the process of EMT, transforming growth factor beta (TGFbeta) is believed to play a central role in the process. Unlike fibrotic lesions in kidney or other tissues where myofibroblasts are generated from both fibroblasts and epithelial cells, fibrotic lesions in the eye crystalline lens are derived only from lens epithelial cells without contamination of fibroblast-derived myofibroblasts. Thus, this tissue is suitable to investigate detailed mechanisms of EMT and subsequent tissue fibrosis. EMT in retinal pigment epithelium is involved in the development of another ocular fibrotic disease, proliferative vitreoretinopathy, a fibrosis in the retina. EMT-related signal transduction cascades, i. e., TGFbeta/Smad, are a target to prevent or treat unfavorable ocular tissue fibrosis, e. g., fibrotic diseases in the crystalline lens or retina, as well as possibly in other organs.
Saika
Shizuya
S
Department of Ophthalmology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-0012, Japan. shizuya@wakayama-med.ac.jp
Yamanaka
Osamu
O
Flanders
Kathleen C
KC
Okada
Yuka
Y
Miyamoto
Takeshi
T
Sumioka
Takayoshi
T
Shirai
Kumi
K
Kitano
Ai
A
Miyazaki
Ken-ichi
K
Tanaka
Sai-ichi
S
Ikeda
Kazuo
K
D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects*; D005109:Extracellular Matrix / Q000473:pathology; D005128:Eye Diseases / Q000473:pathology* / Q000517:prevention & control*; D005131:Eye Injuries / Q000188:drug therapy / Q000473:pathology; D005355:Fibrosis; D015316:Genetic Therapy; D006801:Humans; D008648:Mesoderm / Q000187:drug effects*; D013508:Ophthalmologic Surgical Procedures; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology
D051900:Smad3 Protein; D016212:Transforming Growth Factor beta