Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
International Ophthalmology
Published in: International Ophthalmology 6/2020

01-06-2020 | Glaucoma | Original Paper

Silencing of p53 reduces cell migration in human Tenon's fibroblasts induced by TGF-β

Authors: Ning Li, Ran Zhang

Published in: International Ophthalmology | Issue 6/2020

Login to get access

Abstract

Purpose

Growth factors are considered as key molecules that participating in fibrosis formation. This research aimed to clarify potential effects of p53 on regulation of transforming growth factor β (TGF-β) and fibrosis formation and investigate the associated mechanisms.

Methods

Vimentin was examined to identify human Tenon's fibroblasts (HTFs). p53-targeting small interfere RNA (siRNA) was synthesis and transfected into HTFs. Real-time PCR assay was utilized to evaluate p53 and microRNA-29b (miR-29b) expression. Immunocytochemical assay was used to observe TGF-β expression. The wound healing assay was conducted to evaluate migration of HTFs. Dual-luciferase assay was employed to identify interaction between p53 and miR-29b in HTFs.

Results

Vimentin was extensively distributed in HTFs cells. HTFs at density of 5 × 104 cells/ml and 6 days exhibited the best growth. The p53 level in TGF-β treatment group was significantly higher compared to that in blank group (p < 0.01). miR-29b level in siRNA targeting p53 group was significantly increased compared to that in blank group (p < 0.01). siRNA targeting p53 could significantly inhibit HTFs migration compared to that in single TGF-β treating HTFs group (p < 0.01). Relative luciferase activity was significantly increased in p53 overexpressed HTFs compared to that in cells transfected with empty pcDNA3.0 plasmid (p < 0.01).

Conclusions

p53 inhibited expression of TGF-β, suppressed HTFs migration and inhibited HTFs growth, by reducing miR-29b expression and interacting with miR29b gene in HTFs.
Literature
1.
Resnikoff S, Pascolini D, Etya'ale D et al (2004) Global data on visual impairment in the year 2002. Bull World Health Org 82:844–851PubMed
2.
Moschos MM, Nitoda E, Fenzel I et al (2019) Prognostic factors of pediatric glaucoma: a retrospective study. Int Ophthalmol 39:359–373CrossRef
3.
Crawley L, Zamir SM, Cordeiro MF et al (2012) (201) Clinical options for the reduction of elevated intraocular pressure. Ophthalmol Eye Dis 4:43–64CrossRef
4.
Merritt SR, Velasguez G, von Recum HA (2013) Adjustable release of mitomycin C for inhibition of scar tissue formation after filtration surgery. Exp Eye Res 116:9–16CrossRef
5.
Sharma A, Anumanthan G, Reyes M et al (2016) Epigenetic modification prevents excessive wound healing and scar formation after glaucoma filtration surgery. Investig Ophthalmol Vis Sci 57:3381–3389CrossRef
6.
Yamanaka O, Kitano-Izutani A, Tmoyose K et al (2015) Pathobiology of wound healing after glaucoma filtration surgery. BMC Ophthalmol 157:19–25
7.
Bao P, Kodra A, Tomic-Canic M et al (2009) The role of vascular endothelial growth factor in wound healing. J Surg Res 153:347–358CrossRef
8.
Cordeiro MF, Gay JA, Khaw PT (1999) Human anti-transforming growth factor beta 2 antibody: a new glaucoma anti-scarring agent. Invest Ophthalmol Vis Sci 40:2225–2234PubMed
9.
Rodriguez-Agirretxe I, Garcia I, Soria J et al (2012) Custom RT-qPCR array for glaucoma filtering surgery prognosis. PLoS ONE 12:e0174559CrossRef
10.
Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114CrossRef
11.
Zhang X, Pan Y, Fu H et al (2019) MicroRNA-205 and microRNA-338-3p reduces cell apoptosis in prostate carcinoma tissue and LNCaP prostate carcinoma by directly targeting the B-cell lymphoma 2 (Bcl-2) gene. Med Sci Monit 25:1122–1132CrossRef
12.
Li N, Cui J, Duan X et al (2012) Suppression of type I collagen expression by miR-29b via PI3K, Akt and Sp1 pathway in human Tenon's fibroblasts. Investig Ophthalmol Vis Sci 53:1670–1678CrossRef
13.
Li Z, Hassan MQ, Jafferji M et al (2009) Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem 284:15676–15684CrossRef
14.
Hong B, van den Heuvel AP, Prabhu VV et al (2014) Targeting tumor suppressor p53 for cancer therapy: strategies, challenges and opportunities. Curr Drug Targets 15:80–89CrossRef
15.
Yan L, Lu XY, Wang CM et al (2007) Association between p53 gene codon 72 polymorphism and keloid in Chinese population. Zhonghua Zheng Xing Wai Ke Za Zhi 23:428–430PubMed
16.
Ghosh AK, Quaggin SE, Vaughan DE (2013) Molecular basis of organ fibrosis: potential therapeutic approaches. Exp Biol Med 238:461–481CrossRef
17.
Md Noh SM, Sheikh Abdul Kadir SH, Bannur ZM et al (2014) Effects of ranibizumab on the extracellular matrix production by human Tenon's fibroblast. Exp Eye Res 127:236–242CrossRef
18.
Deng F, Hu H, Chen M et al (2012) Generation of induced pluripotent stem cells form human Tenon's capsule fibroblasts. Mol Vis 18:2871–2881PubMedPubMedCentral
19.
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−△△ct method. Methods 25:402–408PubMed
20.
Delic S, Lottmann N, Stelzl A et al (2014) MiR-328 promotes glioma cell invasion via SFRP-1-dependent Wnt-signaling activation. Neuro Oncol 16:179–190CrossRef
21.
Park G, Yoon BS, Moon JH et al (2008) Green tea polyphenol epigallocatechin-3-gallate suppresses collagen production and proliferation in keloid fibroblasts via inhibition of the STAT3-signaling pathway. J Investig Dermatol 128:2429–2441CrossRef
22.
Margadant C, Sonnenberg A (2010) Integrin-TGF-beta crosstalk in fibrosis, cancer and wound healing. EMBO Rep 11:97–105CrossRef
23.
Walraven M, Gouverneur M, Middelkoop E et al (2014) Altered TGF-beta signaling in fetal fibroblasts: what is known about the underlying mechanisms? Wound Repair Regen 22:3013CrossRef
24.
Ran W, Zhu D, Feng Q (2015) TGF-beta2 stimulates Tenon's capsule fibroblast proliferation in patients with glaucoma via suppression of miR-29b expression regulated by Nrf2. Int J Clin Exp Pathol 8:4799–4806PubMedPubMedCentral
25.
Shimizu H, Yisireyili M, Nishijima F et al (2013) Indoxyl sulfate enhances p53-TGF-beta1-Smad3 pathway in proximal tubular cells. Am J Neuphrol 37:97–103CrossRef
26.
Du XY, Liu X, Wang ZJ et al (2017) SLPI promotes the gastric cancer growth and metastasis by regulating the expression of p53, Bcl-2 and caspase-8. Eur Rev Med Pharmacol Sci 21:1495–1501PubMed
27.
Lei C, Zhou X, Pang Y et al (2015) TGF-beta signaling prevents pancreatic beta cell death after proliferation. Cell Prolif 48:356–362CrossRef
28.
Zhao H, Wilkie T, Deol Y et al (2015) miR-29b defines the pro-/anti-proliferative effects of S100A7 in breast cancer. Mol Cancer 14:11CrossRef
29.
OhAinmhire E, Quartuccio SM, Cheng W et al (2014) Mutation or loss of p53 differentially modifies TGF-β action in ovarian cancer. PLoS ONE 9:e89553CrossRef
30.
Mott JL, Kurita S, Cazanave SC et al (2010) Transcriptional suppression of mir-29b-1/mir-29a promoter by c-Myc, hedgehog, and NF-kappa B. J Cell Biochem 110:1155–1164CrossRef
Metadata
Title
Silencing of p53 reduces cell migration in human Tenon's fibroblasts induced by TGF-β
Authors
Ning Li
Ran Zhang
Publication date
01-06-2020
Publisher
Springer Netherlands
Keyword
Glaucoma
Published in
International Ophthalmology / Issue 6/2020
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI
https://doi.org/10.1007/s10792-020-01320-9

Other articles of this Issue 6/2020

International Ophthalmology 6/2020 Go to the issue

Review

Antigen-presenting cells in ocular surface diseases

Original Paper

Anterior segment parameters in Behçet’s patients with ocular involvement

Original Paper

Corneal topography, anterior segment and high-order aberration assessments in children with ≥ 2 diopter astigmatism

Original Paper

Outcome of sutured scleral fixated intraocular lens in Marfan syndrome in pediatric eyes

Original Paper

Flattened flanged intrascleral intraocular lens fixation technique

Original Paper

Management of moderate-to-severe dry eye disease using chitosan-N-acetylcysteine (Lacrimera®) eye drops: a retrospective case series