title: FOXC1 in human trabecular meshwork cells is involved in regulatory pathway that includes miR-204, MEIS2, and ITGβ1.
abstract: Forkhead box C1 (FOXC1) is a transcription factor that affects eye development. FOXC1 is implicated in the etiology of glaucoma because mutations in the gene are among the causes of Axenfeld-Rieger syndrome which is often accompanied by glaucoma. Glaucoma is the second leading cause of blindness. It is a complex disorder whose genetic basis in most patients remains unknown. Microarrays expression analysis was performed to identify genes in human trabecular meshwork (TM) primary cultures that are affected by FOXC1 and genes that may have roles in glaucoma. This represents the first genome wide analysis of FOXC1 target genes in any tissue. FOXC1 knock down by siRNAs affected the expression of 849 genes. Results on selected genes were confirmed by real time PCR, immunoblotting, and dual luciferase reporter assays. Observation of MEIS2 as a FOXC1 target and consideration of FOXC1 as a potential target of miR-204 prompted testing the effect of this micro RNA on expression of FOXC1 and several genes identified by array analysis as FOXC1 target genes. It was observed that miR-204 caused decreased expression of FOXC1 and the FOXC1 target genes CLOCK, PLEKHG5, ITGβ1, and MEIS2 in the TM cultures. Expression of CLOCK, PLEKHG5, ITGβ1 has not previously been reported to be affected by miR-204. The data suggest existence of a complex regulatory pathway in the TM part of which includes interactions between FOXC1, miR-204, MEIS2, and ITGβ1. All these molecules are known to have TM relevant functions, and the TM is strongly implicated in the etiology of glaucoma.
authors.affiliation: School of Biology, Damghan University, Damghan, Iran.
authors.forename: Seyed Hassan
authors.initials: SH
authors.lastname: Paylakhi
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Moazzeni
authors.forename: Shahin
authors.initials: S
authors.lastname: Yazdani
authors.forename: Paniz
authors.initials: P
authors.lastname: Rassouli
authors.forename: Ehsan
authors.initials: E
authors.lastname: Arefian
authors.forename: Elham
authors.initials: E
authors.lastname: Jaberi
authors.forename: Emad Heidari
authors.initials: EH
authors.lastname: Arash
authors.forename: Ahmad Sadighi
authors.initials: AS
authors.lastname: Gilani
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.forename: Craig
authors.initials: C
authors.lastname: April
authors.forename: Sadaf
authors.initials: S
authors.lastname: Amin
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Suri
authors.forename: Elahe
authors.initials: E
authors.lastname: Elahi
mesh_terms: D000328:Adult; D000368:Aged; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D014129:Trabecular Meshwork / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D020662:Guanine Nucleotide Exchange Factors; D018398:Homeodomain Proteins; D019012:Integrin beta1; C491172:MEIS2 protein, human; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; C522397:PLEKHG5 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D008156:Luciferases; D056926:CLOCK Proteins; C538943:CLOCK protein, human