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Published on: July 22, 2022
Tetrandrine suppresses activation of human subconjunctival fibroblasts in vitro
Ai Kitano1, Osamu Yamanaka, Kazuo Ikeda
1Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. aikitano@wakayamamed.ac.jp
Purpose:
To investigate the effect of tetrandrine on activation of human subconjunctival fibroblasts (SCFs) in vitro.
Methods:
Effects of tetrandrine on proliferation, matrix expression, myofibroblast generation, and cell migration of SCF were examined in SCF cultures. Tetrandrine effect on TGFbeta 1/Smad2 signal and Smad7 expression was examined. Migration was evaluated by in vitro defect closure in a monolayer cell culture. Western blotting and immunocytochemistry were used.
Results:
Tetrandrine suppressed wound-induced cell migration (defect closure) and myofibroblast generation, but not cell proliferation in SCF cultures. It also decreased expression of fibronectin, collagen I, and alpha SMA. Adding tetrandrine increased protein level of Smad7 and suppressed Smad2 signal.
Conclusion:
Tetrandrine suppresses Smad2 signal and fibrogenic responses in SCFs in association with Smad7 up-regulation, suggesting its potential therapeutic value to prevent excess scarring/fibrosis in conjunctiva following trabeculectomy or in patients with severe conjunctival inflammation.
Insights
Tetrandrine inhibits human subconjunctival fibroblast activation, reducing scarring. This compound suppresses cell migration and myofibroblast generation by modulating the TGF-beta/Smad2 signaling pathway.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Conjunctival fibrosis can lead to complications after ocular surgery like trabeculectomy.
- Subconjunctival fibroblasts (SCFs) play a key role in scar formation.
- Identifying therapeutic agents to modulate SCF activation is crucial for preventing ocular scarring.
Purpose of the Study:
- To investigate the effects of tetrandrine on the activation of human subconjunctival fibroblasts (SCFs) in vitro.
- To explore tetrandrine's impact on key fibrogenic processes in SCFs.
- To elucidate the molecular mechanisms underlying tetrandrine's action on SCFs.
Main Methods:
- SCFs were cultured to assess the effects of tetrandrine on proliferation, matrix protein expression, myofibroblast differentiation, and cell migration.
- Western blotting and immunocytochemistry were employed to analyze the TGF-beta 1/Smad2 signaling pathway and Smad7 expression.
- In vitro wound healing assays were used to evaluate cell migration.
Main Results:
- Tetrandrine significantly suppressed wound-induced cell migration and myofibroblast generation in SCFs.
- The expression of extracellular matrix components, including fibronectin, collagen I, and alpha-smooth muscle actin (α-SMA), was decreased by tetrandrine.
- Tetrandrine treatment led to increased Smad7 protein levels and suppressed the Smad2 signaling pathway.
Conclusions:
- Tetrandrine effectively inhibits fibrogenic responses in human subconjunctival fibroblasts.
- The mechanism involves the suppression of the Smad2 signaling pathway, associated with an upregulation of Smad7.
- Tetrandrine shows potential as a therapeutic agent to prevent conjunctival scarring and fibrosis following glaucoma surgery or in inflammatory conditions.
