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Article: OMICs approaches-assisted identification of macrophages-derived MIP-1γ as the therapeutic target of botanical products TNTL in diabetic retinopathy

TitleOMICs approaches-assisted identification of macrophages-derived MIP-1γ as the therapeutic target of botanical products TNTL in diabetic retinopathy
Authors
KeywordsDiabetic retinopathy
Endothelial dysfunctions
Inflammation
MIP1γ/CCR1 axis
Retina macrophages
Tang-Ning-Tong-Luo
Issue Date2019
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biosignaling.com/home/
Citation
Cell Communication and Signaling, 2019, v. 17, p. article no. 81 How to Cite?
AbstractBackground Inflammatory reaction in the dysfunction of retinal endotheliocytes has been considered to play a vital role in diabetic retinopathy (DR). Anti-inflammatory therapy so far gains poor outcome as DR treatment. This study aims to identify a novel therapeutic target of DR from the OMICs studies of a traditional anti-DR botanical products TNTL. Methods Hyperglycemic mice were treated with TNTL. The anti-hyperglycemic effect of TNTL was validated to confirm the biological consistency of the herbal products from batches. Improvement of DR by TNTL was examined by various assays on the retina. Next-generation transcriptome sequencing and cytokine array was used to identify the therapeutic targets. In vitro study was performed to validate the target. Results We observed that TNTL at its high doses possessed anti-hyperglycemic effect in murine type I diabetic model, while at its doses without reducing blood glucose, it suppressed DR incidence. TNTL restored the blood-retina barrier integrity, suppressed retinal neovascularization, and attenuated the retinal ganglion cell degeneration. Transcriptomic analysis on the retina tissue of hyperglycemic mice with or without TNTL revealed that the inflammatory retina microenvironment was significantly repressed. TNTL treatment suppressed pro-inflammatory macrophages in the retina, which resulted in the inactivation of endothelial cell migration, restoration of endothelial cell monolayer integrity, and prevention of leakage. Cytokine array analysis suggested that TNTL could significantly inhibit the secretion of MIP1γ from pro-inflammatory macrophages. Prevention of endothelial dysfunction by TNTL may be mediated by the inhibition of MIP1γ/CCR1 axis. More specifically, TNTL suppressed MIP1γ release from pro-inflammatory macrophages, which in turn inhibited the activation of CCR1-associated signaling pathways in endothelial cells. Conclusion Our findings demonstrated that TNTL might be an alternative treatment to DR, and the primary source of potential drug candidates against DR targeting MIP1γ/CCR1 axis in the retinal microenvironment.
Persistent Identifierhttp://hdl.handle.net/10722/274487
ISSN
2023 Impact Factor: 8.2
2023 SCImago Journal Rankings: 2.308
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, N-
dc.contributor.authorZhang, C-
dc.contributor.authorXu, Y-
dc.contributor.authorLi, S-
dc.contributor.authorTan, HYH-
dc.contributor.authorXia, W-
dc.contributor.authorFeng, Y-
dc.date.accessioned2019-08-18T15:02:41Z-
dc.date.available2019-08-18T15:02:41Z-
dc.date.issued2019-
dc.identifier.citationCell Communication and Signaling, 2019, v. 17, p. article no. 81-
dc.identifier.issn1478-811X-
dc.identifier.urihttp://hdl.handle.net/10722/274487-
dc.description.abstractBackground Inflammatory reaction in the dysfunction of retinal endotheliocytes has been considered to play a vital role in diabetic retinopathy (DR). Anti-inflammatory therapy so far gains poor outcome as DR treatment. This study aims to identify a novel therapeutic target of DR from the OMICs studies of a traditional anti-DR botanical products TNTL. Methods Hyperglycemic mice were treated with TNTL. The anti-hyperglycemic effect of TNTL was validated to confirm the biological consistency of the herbal products from batches. Improvement of DR by TNTL was examined by various assays on the retina. Next-generation transcriptome sequencing and cytokine array was used to identify the therapeutic targets. In vitro study was performed to validate the target. Results We observed that TNTL at its high doses possessed anti-hyperglycemic effect in murine type I diabetic model, while at its doses without reducing blood glucose, it suppressed DR incidence. TNTL restored the blood-retina barrier integrity, suppressed retinal neovascularization, and attenuated the retinal ganglion cell degeneration. Transcriptomic analysis on the retina tissue of hyperglycemic mice with or without TNTL revealed that the inflammatory retina microenvironment was significantly repressed. TNTL treatment suppressed pro-inflammatory macrophages in the retina, which resulted in the inactivation of endothelial cell migration, restoration of endothelial cell monolayer integrity, and prevention of leakage. Cytokine array analysis suggested that TNTL could significantly inhibit the secretion of MIP1γ from pro-inflammatory macrophages. Prevention of endothelial dysfunction by TNTL may be mediated by the inhibition of MIP1γ/CCR1 axis. More specifically, TNTL suppressed MIP1γ release from pro-inflammatory macrophages, which in turn inhibited the activation of CCR1-associated signaling pathways in endothelial cells. Conclusion Our findings demonstrated that TNTL might be an alternative treatment to DR, and the primary source of potential drug candidates against DR targeting MIP1γ/CCR1 axis in the retinal microenvironment.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biosignaling.com/home/-
dc.relation.ispartofCell Communication and Signaling-
dc.rightsCell Communication and Signaling. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectDiabetic retinopathy-
dc.subjectEndothelial dysfunctions-
dc.subjectInflammation-
dc.subjectMIP1γ/CCR1 axis-
dc.subjectRetina macrophages-
dc.subjectTang-Ning-Tong-Luo-
dc.titleOMICs approaches-assisted identification of macrophages-derived MIP-1γ as the therapeutic target of botanical products TNTL in diabetic retinopathy-
dc.typeArticle-
dc.identifier.emailWang, N: ckwang@hku.hk-
dc.identifier.emailLi, S: lishaha@hku.hk-
dc.identifier.emailTan, HYH: hyhtan@hku.hk-
dc.identifier.emailFeng, Y: yfeng@hku.hk-
dc.identifier.authorityWang, N=rp02075-
dc.identifier.authorityFeng, Y=rp00466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s12964-019-0396-5-
dc.identifier.pmid31331327-
dc.identifier.scopuseid_2-s2.0-85069762958-
dc.identifier.hkuros301069-
dc.identifier.volume17-
dc.identifier.spagearticle no. 81-
dc.identifier.epagearticle no. 81-
dc.identifier.isiWOS:000476737400001-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl1478-811X-

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