Enhanced functional properties of human limbal stem cells by inhibition of the miR‐31/<scp>FIH</scp>‐1/P21 axis

Liu, Zhiping; Zhan, Wei-Jiao; Zeng, Mingbing; Chen, Jinghong; Zou, Huyong; Min, Zhiqun

doi:10.1111/aos.13503

Cited by 5 publications

(4 citation statements)

References 23 publications

(40 reference statements)

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“…To the best of our knowledge, other non-coding RNAs have only been indirectly associated with the regulation of FIH to date and are therefore not further discussed. microRNA-31 (miR-31) regulates FIH mRNA in head and neck squamous cell carcinoma (HNSCC) (90), keratinocytes (124), corneal epithelial cells (123), limbal (corneal epithelial) stem cells (95), keloid (193), lung cancer cell lines (198), non-small cell lung cancer (NSCLC) (45), and (when applied in exosomes as therapeutic) in diabetic wounds (54). miR-31 reduces FIH mRNA (and thus FIH protein) levels by targeting its 3'-untranslated region (3'-UTR) (45, 90).…”

Section: Transcriptionmentioning

confidence: 99%

“…miR-31 reduces FIH mRNA (and thus FIH protein) levels by targeting its 3'-untranslated region (3'-UTR) (45, 90). miR-31-mediated reduction of FIH has been associated with favouring HNSCC development (90), promoting keratinocyte differentiation (124), increasing glycogen synthesis in corneal epithelial cells (123), reducing stemness in limbal stem cells (95), decreasing apoptosis while enhancing cell proliferation in keloid tissue (193), contributing to the Warburg effect in lung cancer cell lines (198), supporting gefitinib (an inhibitor of the epidermal growth factor receptor) resistance in NSCLC (45), and with promoting diabetic wound healing (54) in a HIF-dependent and/or HIF-independent manner.…”

Section: Transcriptionmentioning

confidence: 99%

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The Asparagine Hydroxylase FIH: A Unique Oxygen Sensor

Volkova

Jucht

Wenger

et al. 2022

Antioxidants & Redox Signaling

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Significance: Limited oxygen availability (hypoxia) commonly occurs in a range of physiological and pathophysiological conditions, including embryonic development, physical exercise, inflammation, and ischemia. It is thus vital for cells and tissues to monitor their local oxygen availability to be able to adjust in case the oxygen supply is decreased. The cellular oxygen sensor factor inhibiting hypoxiainducible factor (FIH) is the only known asparagine hydroxylase with hypoxia sensitivity. FIH uniquely combines oxygen and peroxide sensitivity, serving as an oxygen and oxidant sensor. Recent Advances: FIH was first discovered in the hypoxia-inducible factor (HIF) pathway as a modulator of HIF transactivation activity. Several other FIH substrates have now been identified outside the HIF pathway. Moreover, FIH enzymatic activity is highly promiscuous and not limited to asparagine hydroxylation. This includes the FIH-mediated catalysis of an oxygen-dependent stable (likely covalent) bond formation between FIH and selected substrate proteins (called oxomers [oxygen-dependent stable protein oligomers]). Critical Issues: The (patho-)physiological function of FIH is only beginning to be understood and appears to be complex. Selective pharmacologic inhibition of FIH over other oxygen sensors is possible, opening new avenues for therapeutic targeting of hypoxia-associated diseases, increasing the interest in its (patho-)physiological relevance. Future Directions: The contribution of FIH enzymatic activity to disease development and progression should be analyzed in more detail, including the assessment of underlying molecular mechanisms and relevant FIH substrate proteins. Also, the molecular mechanism(s) involved in the physiological functions of FIH remain(s) to be determined. Furthermore, the therapeutic potential of recently developed FIH-selective pharmacologic inhibitors will need detailed assessment. Antioxid.

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Section: Transcriptionmentioning

confidence: 99%

Section: Transcriptionmentioning

confidence: 99%

The Asparagine Hydroxylase FIH: A Unique Oxygen Sensor

Volkova

Jucht

Wenger

et al. 2022

Antioxidants & Redox Signaling

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“…Limbal stem cell deficiency may cause recurrent corneal epithelial erosions, inflammatory reactions and ingrowth of fibro-vascular tissue onto the corneal surface. Removal of the diseased tissue and transplantation of ex vivo engineered epithelium may restore the integrity of the corneal surface (Pellegrini et al 1997;Nakamura et al 2004;Sangwan et al 2011;Pathak et al 2013;Romero et al 2014;Zakaria et al 2014;Ljubimov & Saghizadeh 2015;Szab o et al 2015;Etxebarria et al 2017;Liu et al 2017). Removal of the diseased tissue and transplantation of ex vivo engineered epithelium may restore the integrity of the corneal surface (Pellegrini et al 1997;Nakamura et al 2004;Sangwan et al 2011;Pathak et al 2013;Romero et al 2014;Zakaria et al 2014;Ljubimov & Saghizadeh 2015;Szab o et al 2015;Etxebarria et al 2017;Liu et al 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Clinical symptoms include ocular pain and loss of vision (Tseng 1996;Dua et al 2000). Removal of the diseased tissue and transplantation of ex vivo engineered epithelium may restore the integrity of the corneal surface (Pellegrini et al 1997;Nakamura et al 2004;Sangwan et al 2011;Pathak et al 2013;Romero et al 2014;Zakaria et al 2014;Ljubimov & Saghizadeh 2015;Szab o et al 2015;Etxebarria et al 2017;Liu et al 2017). For such engineering, a sample containing limbal epithelium is removed from the donor eye, and cultures may be initiated by the suspension culture technique or by the explant culture technique.…”

Section: Introductionmentioning

confidence: 99%

Levels of oxidative DNA damage are low in ex vivo engineered human limbal epithelial tissue

Lorenzo

Berg

Ringvold

et al. 2018

Acta Ophthalmologica

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Purpose To examine levels of oxidative DNA base damage and expression of selected genes and proteins related to DNA damage repair in human limbal epithelium engineered ex vivo. Methods Cells were expanded from limbal tissue on cell culture‐treated inserts in medium containing fetal bovine serum, recombinant growth factors, hormones and cholera toxin (COM) and in medium with human serum as the single growth‐promoting additive (HS). Cells were analysed after two, three and four weeks in culture for DNA strand breaks and oxidized purine bases (Comet assay using the enzyme formamidopyrimidine DNA glycosylase, Fpg) and for expression of DNA repair enzymes APE1, OGG1 and Polβ by in situ hybridization (ISH) and by immunohistochemistry (IHC). Results Levels of strand breaks were substantial while levels of net Fpg‐sensitive sites (8‐oxoguanine and ring‐opened FaPy bases) were relatively low in cells engineered in COM and in HS. Both types of medium were found to support expression of base excision repair (BER) enzymes APE1, OGG1 and Polβ at the gene level. At the protein level, expression of APE1 and OGG1 was noticeable in both conditions while expression of Polβ was low. Conclusion Our findings indicate low levels of oxidative stress and/or efficient DNA purine base damage repair in human limbal epithelium engineered in a medium with human serum as the single growth‐promoting additive as well as in traditional medium with xenobiotics.

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Abnormal neovascular and proliferative conjunctival phenotype in limbal stem cell deficiency is associated with altered microRNA and gene expression modulated by PAX6 mutational status in congenital aniridia

et al. 2021

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Enhanced functional properties of human limbal stem cells by inhibition of the miR‐31/FIH‐1/P21 axis

Abstract: ES culture supernatant (ESC-CM) regulates the fate of LSCs in part by inhibiting the miR-31/FIH-1/P21 axis. This study may have a high impact on the expansion of LSCs in regenerative medicine, especially for ocular surface reconstruction.

Cited by 5 publications

References 23 publications

The Asparagine Hydroxylase FIH: A Unique Oxygen Sensor

The Asparagine Hydroxylase FIH: A Unique Oxygen Sensor

Levels of oxidative DNA damage are low in ex vivo engineered human limbal epithelial tissue

Abnormal neovascular and proliferative conjunctival phenotype in limbal stem cell deficiency is associated with altered microRNA and gene expression modulated by PAX6 mutational status in congenital aniridia

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