Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic retinopathy

Wenjun Wang, Qing Wang, Danyang Wan, Yue Sun, Lin Wang, Hong Chen, Chengyu Liu, Robert B. Petersen, Jianshuang Li, Weili Xue, Ling Zheng, Kun Huang

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Autophagy plays critical and complex roles in many human diseases, including diabetes and its complications. However, the role of autophagy in the development of diabetic retinopathy remains uncertain. Core histone modifications have been reported involved in the development of diabetic retinopathy, but little is known about the histone variants. Here, we observed increased autophagy and histone HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG proteins, then promotes autophagy in cultured retinal cell line. Histone HIST1H1C overexpression also promotes inflammation and cell toxicity in vitro. Knockdown of histone HIST1H1C reduces both the basal and stresses (including high glucose)-induced autophagy, and inhibits high glucose induced inflammation and cell toxicity. Importantly, AAV-mediated histone HIST1H1C overexpression in the retinas leads to increased autophagy, inflammation, glial activation and neuron loss, similar to the pathological changes identified in the early stage of diabetic retinopathy. Furthermore, knockdown of histone Hist1h1c by siRNA in the retinas of diabetic mice significantly attenuated the diabetes-induced autophagy, inflammation, glial activation and neuron loss. These results indicate that histone HIST1H1C may offer a novel therapeutic target for preventing diabetic retinopathy.

Original languageEnglish
Pages (from-to)941-954
Number of pages14
JournalAutophagy
Volume13
Issue number5
DOIs
StatePublished - May 4 2017

Keywords

  • H4K16Ac
  • autophagy
  • cell toxicity
  • diabetic retinopathy
  • histone HIST1H1C
  • inflammation

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