Heme oxygenase‑1 alleviates advanced glycation end product‑induced oxidative stress, inflammatory response and biological behavioral disorders in rat dermal fibroblasts

Li,Qingling; Liang,Shangyan; Lai,Qianwei; Shen,Lishan; Zhang,Yong; Guo,Ruomi

doi:10.3892/etm.2021.10646

Heme oxygenase‑1 alleviates advanced glycation end product‑induced oxidative stress, inflammatory response and biological behavioral disorders in rat dermal fibroblasts

Authors:
- Qingling Li
- Shangyan Liang
- Qianwei Lai
- Lishan Shen
- Yong Zhang
- Ruomi Guo
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Affiliations: Department of VIP Medical Service Center, The Third Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Radiology, The Third Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Nuclear Medicine, The Third Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: August 24, 2021 https://doi.org/10.3892/etm.2021.10646
Article Number: 1212
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Advanced glycation end products (AGEs) are involved in delaying the wound healing of diabetic foot ulcers. The present study investigated the effects of heme oxygenase‑1 (HO‑1) on oxidative stress, inflammatory insult and biological behaviors in rat dermal fibroblasts in the presence of AGEs. Rat dermal fibroblasts were cultured in the presence of AGEs (100 µg/ml), glucose (1.0 g/l or 4.5 g/l), hemin (5 µM) and chromium mesoporphyrin (CrMP; 20 µM). A bilirubin kit, reverse transcription‑quantitative PCR and western blotting were used to measure the activity and mRNA and protein levels of HO‑1, respectively. ELISA kits were used to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), 8‑hydroxydeoxyguanosine (8‑OHdG), TNF‑α, IL‑6, IL‑1β and the viability and collagen (hydroxyproline) secretion of fibroblasts. Cell proliferation and apoptosis were measured via flow cytometry. The scratch test was performed to evaluate cell migration. The results revealed that AGEs resulted in oxidative stress, inflammatory response and biological behavioral disorders in fibroblasts, while worsened functional disorders were caused by the combination of AGEs and high‑glucose treatment. Hemin treatment induced sustained high HO‑1 expression, decreased the levels of ROS, MDA, 8‑OHdG, TNF‑α, IL‑6, IL‑1β and cell apoptosis, and increased cellular collagen synthesis, viability, proliferation and migration, whereas CrMP abolished the effects of hemin. It was observed that high HO‑1 expression reversed the AGE‑induced oxidative stress, inflammatory response and biological behavioral disorders in fibroblasts, but fibroblast function did not return to that observed under normal glucose levels. In conclusion, it was demonstrated that hemin treatment induced high HO‑1 expression. HO‑1 reduced the AGE‑induced functional disorders in fibroblasts and may accelerate the healing of diabetic wounds by improving fibroblast biological behaviors and reducing the oxidative stress and inflammatory response.

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