Dataset Information

Assessing the protective effects of cryptotanshinone on CoCl2‑induced hypoxia in RPE cells.

ABSTRACT: The development of several retinal diseases is closely related to hypoxia. As a component of the Traditional Chinese medicine Salvia miltiorrhiza, the effects of cryptotanshinone (CT) on retinal cells under hypoxic conditions are not well understood. The aim of the present study was to explore how CT exerted its protective effects on retinal pigment epithelium (RPE) cells under hypoxic conditions induced by cobalt chloride (CoCl2). The effects of CT were investigated using a Cell Counting Kit‑8 assay, Annexin V‑FITC/PI staining, reverse transcription‑quantitative PCR and western blotting in ARPE‑19 cells. CT (10 and 20 µM) reduced the CoCl2‑induced increase in vascular endothelial growth factor expression and hypoxia‑inducible transcription factor‑1α expression in ARPE‑19 cells. Additionally, CT alleviated hypoxia‑induced apoptosis by regulating Bcl‑2 and Bax protein expression. CT treatment also reduced the increase in the mRNA levels of IL‑6, IL‑1β and TNF‑α induced by CoCl2. In summary, CT may protect RPE cells against apoptosis and inflammation in CoCl2‑induced hypoxia, and these results warrant further in vivo study into its value as a drug for treating hypoxic eye diseases.

SUBMITTER: Gu Y

PROVIDER: S-EPMC8404095 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Assessing the protective effects of cryptotanshinone on CoCl2‑induced hypoxia in RPE cells.

Gu Yu Y Liu Weiming W Liu Gaoqin G Li Xin X Lu Peirong P

Molecular medicine reports 20210826 4

The development of several retinal diseases is closely related to hypoxia. As a component of the Traditional Chinese medicine Salvia miltiorrhiza, the effects of cryptotanshinone (CT) on retinal cells under hypoxic conditions are not well understood. The aim of the present study was to explore how CT exerted its protective effects on retinal pigment epithelium (RPE) cells under hypoxic conditions induced by cobalt chloride (CoCl2). The effects of CT were investigated using a Ce ...[more]

PMID: 34435647

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Project description:BackgroundThe retinal pigment epithelium (RPE) has the potential to regenerate the entire neuroretina upon retinal injury in amphibians. In contrast, this regenerative capacity has been lost in mammals. The reprogramming of differentiated somatic cells into induced pluripotent stem cells (iPSCs) by viral transduction of exogenous stem cell factors has triggered a revolution in regenerative medicine. However, the risks of potential mutation(s) caused by random viral vector insertion in host genomes and tumor formation in recipients hamper its clinical application. One alternative is to immortalize adult stem cells with limited potential or to partially reprogram differentiated somatic cells into progenitor-like cells through non-integration protocols.MethodsSphere-induced RPE stem cells (iRPESCs) were generated from adult mouse RPE cells. Their stem cell functionality was studied in a mouse model of retinal degeneration. The molecular mechanism underlying the sphere-induced reprogramming was investigated using microarray and loss-of-function approaches.FindingsWe provide evidence that our sphere-induced reprogramming protocol can immortalize and transform mouse RPE cells into iRPESCs with dual potential to differentiate into cells that express either RPE or photoreceptor markers both in vitro and in vivo. When subretinally transplanted into mice with retinal degeneration, iRPESCs can integrate to the RPE and neuroretina, thereby delaying retinal degeneration in the model animals. Our molecular analyses indicate that the Hippo signaling pathway is important in iRPESC reprogramming.InterpretationThe Hippo factor Yap1 is activated in the nuclei of cells at the borders of spheres. The factors Zeb1 and P300 downstream of the Hippo pathway are shown to bind to the promoters of the stemness genes Oct4, Klf4 and Sox2, thereby likely transactivate them to reprogram RPE cells into iRPESCs. FUND: National Natural Science Foundation of China and the National Institute of Health USA.

Dataset Information

Assessing the protective effects of cryptotanshinone on CoCl2‑induced hypoxia in RPE cells.

Publications

Assessing the protective effects of cryptotanshinone on CoCl<sub>2</sub>‑induced hypoxia in RPE cells.

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