title: Angiotensin II as a morphogenic cytokine stimulating fibrogenesis of human tenon's capsule fibroblasts.
abstract: OBJECTIVE
  To examine the expression of Angiotensin II (Ang II) and its type I, and type II receptors (AT1R, AT2R) in rabbit Tenon's capsule fibroblasts after trabeculectomy, and to investigate the effects of Ang II on cultured human Tenon's capsule fibroblasts (HTFs) proliferation, migration, phenotype transition, and extracellular matrix (ECM) synthesis.
  
  
  METHODS
  In the rabbit, expression of Ang II, AT1R, and AT2R in Tenon's capsule fibroblasts of eyes after trabeculectomy was evaluated by immunohistochemistry. Ang II levels in aqueous humor and plasma were assessed by ELISA. Cultured HTFs, obtained from patients undergoing cataract surgery, were treated with Ang II, TGF-β1, or vehicle control. Cell proliferation and migration were evaluated by Cell Counting Kit-8 and Transwell assay, and wound scratch assay, respectively. Protein expressions of α-smooth muscle actin (α-SMA) and fibronectin (FN) were measured by Western blot and immunofluorescence. Messenger RNA expressions of α-SMA and FN were measured by real-time PCR.
  
  
  RESULTS
  In the rabbit, the expression of Ang II and AT1R increased from 1 day after surgery while AT2R increased from 7 days. In cultured HTFs, Ang II promoted cell proliferation and migration significantly (P < 0.05). Interestingly, the effect of 10(-7) M Ang II was more prominent than higher concentrations (10(-5) M; P < 0.05). Ang II also markedly induced the expression of α-SMA and FN, suggesting a phenotypic transition to myofibroblasts.
  
  
  CONCLUSIONS
  Our results show that trabeculectomy alter the levels of Ang II and its receptors in Tenon's capsule fibroblasts, and that Ang II increase HTFs proliferation, migration, and phenotype transition, suggesting that Ang II may play a role in wound healing after trabeculectomy.
authors.affiliation: Huashan Hospital, Department of Ophthalmology, Fudan University, Shanghai, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Shi
authors.affiliation: Huashan Hospital, Department of Ophthalmology, Fudan University, Shanghai, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Huashan Hospital, Department of Ophthalmology, Fudan University, Shanghai, China.
authors.forename: Shuhao
authors.initials: S
authors.lastname: Fu
authors.affiliation: Huashan Hospital, Department of Ophthalmology, Fudan University, Shanghai, China.
authors.forename: Zhaozeng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Huashan Hospital, Department of Ophthalmology, Fudan University, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Ye
authors.affiliation: Huashan Hospital, Department of Ophthalmology, Fudan University, Shanghai, China.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000804:Angiotensin II / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005901:Glaucoma / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000235:genetics*; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D058475:Tenon Capsule / Q000378:metabolism* / Q000473:pathology; D014130:Trabeculectomy; D014945:Wound Healing
chemical_list: D012333:RNA, Messenger; D000804:Angiotensin II
keywords: Angiotensin II; human Tenon's fibroblasts; migration; phenotype transition; proliferation