ArticleCell communication and signaling : CCS2019
OMICs approaches-assisted identification of macrophages-derived MIP-1γ as the therapeutic target of botanical products TNTL in diabetic retinopathy.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 19 citations in OpenAlex.
- Identification and verification of the key genes, CCR1 and EGR2, in diabetes-associated lipophagy.Scientific reports · 2026Article
- Traditional Chinese medicine in diabetes management: a comprehensive review of mechanisms and therapeutic potential.Frontiers in endocrinology · 2026Review
- The Therapeutic Effect and Mechanism of Traditional Chinese Medicine in Type 2 Diabetes Mellitus and Its Complications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- Identification of immune associated potential molecular targets in proliferative diabetic retinopathy.BMC ophthalmology · 2023Article
- Review
- Asthma and Post-Asthmatic Fibrosis: A Search for New Promising Molecular Markers of Transition from Acute Inflammation to Pulmonary Fibrosis.Biomedicines · 2022Article
- The innate immune system in diabetic retinopathy.Progress in retinal and eye research · 2021Review
- ASK1/p38‑mediated NLRP3 inflammasome signaling pathway contributes to aberrant retinal angiogenesis in diabetic retinopathy.International journal of molecular medicine · 2021Article
- Protective Role of microRNA-200a in Diabetic Retinopathy Through Downregulation of PDLIM1.Journal of inflammation research · 2021Article
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7 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundInflammatory 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.
methodsHyperglycemic 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.
resultsWe 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.
conclusionOur 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.
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