Deletion of hypoxia-inducible factor prolyl 4-hydroxylase 2 in FoxD1-lineage mesenchymal cells leads to congenital truncal alopecia

Rosendahl, Ann-Helen; Monnius, M.; Laitala, Anu; Railo, Antti; Miinalainen, Ilkka; Heljasvaara, Ritva; Mäki, Joni M.; Myllyharju, Johanna

doi:10.1016/j.jbc.2022.101787

Cited by 2 publications

(1 citation statement)

References 78 publications

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“…In mammals, deletion of Stat3 in Foxd1 cell lineage protected mice from kidney fibrosis [35]. Hypoxia-inducible factors (HIFs) regulated genes related to oxygen homeostasis, and lack of Hif-p4h-2 (HIF prolyl-4-hydroxylases) in FoxD1 lineage led to dysregulation of genes involved in the Notch signaling pathway [36]. These results suggest that there is a genetic interaction between mammalian FoxD subfamily members and the JAK-STAT and Notch pathways.…”

Section: Discussionmentioning

confidence: 99%

Functional Analysis of Forkhead Transcription Factor Fd59a in Spermatogenesis of <em>Drosophila melanogaster</em>

Tang,

Pei,

Xiao

et al. 2024

Preprint

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Spermatogenesis is critical for insect reproduction and is regulated by many different genes. In this study, we found that Forkhead transcription factor Fd59a functions as a key factor in spermatogenesis of Drosophila melanogaster. Fd59a contains a conversed Forkhead domain, and it is clustered to the FoxD subfamily with other FoxD members from some insect and vertebrate species. Mutation in Fd59a caused swelling in the apical region of the testis. More importantly, only a few mature sperm were present in the seminal vesicle of Fd59a mutant flies compared to the control flies, and the fertility of Fd59a2/2 mutant males was significantly lower than that of the control flies. Immunofluorescence staining showed that the homeostasis of testis stem cell niche in Fd59a2/2 mutant and Fd59a RNAi flies was disrupted, and apoptosis of sperm bundles was increased. Furthermore, results from RNA-sequencing and qRT-PCR suggest that Fd59a can regulate expression of genes related to reproductive process and cell death. Taken together, our results indicated that Fd59a plays a key role in the spermatogenesis of Drosophila.

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Section: Discussionmentioning

confidence: 99%

Functional Analysis of Forkhead Transcription Factor Fd59a in Spermatogenesis of <em>Drosophila melanogaster</em>

Tang,

Pei,

Xiao

et al. 2024

Preprint

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PHD1-3 oxygen sensors in vivo—lessons learned from gene deletions

Jucht,

Scholz

2024

Pflugers Arch - Eur J Physiol

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Oxygen sensors enable cells to adapt to limited oxygen availability (hypoxia), affecting various cellular and tissue responses. Prolyl-4-hydroxylase domain 1–3 (PHD1-3; also called Egln1-3, HIF-P4H 1–3, HIF-PH 1–3) proteins belong to the Fe2+- and 2-oxoglutarate-dependent dioxygenase superfamily and utilise molecular oxygen (O2) alongside 2-oxoglutarate as co-substrate to hydroxylate two proline residues of α subunits of the dimeric hypoxia inducible factor (HIF) transcription factor. PHD1-3-mediated hydroxylation of HIF-α leads to its degradation and inactivation. Recently, various PHD inhibitors (PHI) have entered the clinics for treatment of renal anaemia. Pre-clinical analyses indicate that PHI treatment may also be beneficial in numerous other hypoxia-associated diseases. Nonetheless, the underlying molecular mechanisms of the observed protective effects of PHIs are only partly understood, currently hindering their translation into the clinics. Moreover, the PHI-mediated increase of Epo levels is not beneficial in all hypoxia-associated diseases and PHD-selective inhibition may be advantageous. Here, we summarise the current knowledge about the relevance and function of each of the three PHD isoforms in vivo, based on the deletion or RNA interference-mediated knockdown of each single corresponding gene in rodents. This information is crucial for our understanding of the physiological relevance and function of the PHDs as well as for elucidating their individual impact on hypoxia-associated diseases. Furthermore, this knowledge highlights which diseases may best be targeted by PHD isoform-selective inhibitors in case such pharmacologic substances become available.

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Deletion of hypoxia-inducible factor prolyl 4-hydroxylase 2 in FoxD1-lineage mesenchymal cells leads to congenital truncal alopecia

Cited by 2 publications

References 78 publications

Functional Analysis of Forkhead Transcription Factor Fd59a in Spermatogenesis of <em>Drosophila melanogaster</em>

Functional Analysis of Forkhead Transcription Factor Fd59a in Spermatogenesis of <em>Drosophila melanogaster</em>

PHD1-3 oxygen sensors in vivo—lessons learned from gene deletions

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