ArticleJournal of molecular medicine (Berlin, Germany)2020
Macrophage migration inhibitory factor is regulated by HIF-1α and cAMP and promotes renal cyst cell proliferation in a macrophage-independent manner.
Article in Journal of molecular medicine (Berlin, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- DNA methylation in adaptation to high-altitude environments and pathogenesis of related diseases.Human genomics · 2025Review
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease: Role in Cystogenesis and Novel Therapeutic Approaches.Biomedicines · 2025Review
- Hypermethylation of BMPR2 and TGF-β Promoter Regions in Tibetan Patients with High-Altitude Polycythemia at Extreme Altitude.Biochemical genetics · 2025Article
- The molecular interplay among gut dysbiosis, adipose tissue, and metabolite-derived damage-associated molecular patterns in metainflammation and atherogenesis.Frontiers in immunology · 2025Review
- Macrophage adaptation to hypoxia: metabolism, migration, and phagocytosis.Frontiers in cellular and infection microbiology · 2025Article
- The roles of macrophage migration inhibitory factor in retinal diseases.Neural regeneration research · 2024Review
- DLGAP5 promotes gallbladder cancer migration and tumor-associated macrophage M2 polarization by activating cAMP.Cancer immunology, immunotherapy : CII · 2023Article
- Urinary Biomarkers in Monitoring the Progression and Treatment of Autosomal Dominant Polycystic Kidney Disease-The Promised Land?Medicina (Kaunas, Lithuania) · 2023Review
- Macrophage Migration Inhibitory Factor (MIF) as a Stress Molecule in Renal Inflammation.International journal of molecular sciences · 2022Review
- Macrophage migration inhibitory factor in acute kidneyinjury.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progressive cyst growth leads to decline of renal function in polycystic kidney disease. Macrophage migration inhibitory factor (MIF) was found to be upregulated in cyst-lining cells in a mouse model of polycystic kidney disease and to promote cyst growth. In addition, MIF can be secreted by tubular cells and may contribute to cyst growth in an autocrine manner. However, the underlying mechanisms leading to induction of MIF in cyst-lining cells remained elusive. Here, we demonstrate that hypoxia-inducible transcription factor (HIF) 1α upregulates MIF in cyst-lining cells in a tubule-specific PKD1 knockout mouse. Pharmacological stabilization of HIF-1α resulted in significant increase of MIF in cyst epithelial cells whereas tubule-specific knockout of HIF-1α prevented MIF upregulation. Identical regulation could be found for ABCA1, which has been shown to act as a transport protein for MIF. Furthermore, we show that MIF and ABCA1 are direct target genes of HIF-1α in human primary tubular cells. Next to HIF-1α and hypoxia, we found MIF being additionally regulated by cAMP which is a strong promotor of cyst growth. In line with these findings, HIF-1α- and cAMP-dependent in vitro cyst growth could be decreased by the MIF-inhibitor ISO-1 which resulted in reduced cyst cell proliferation. In conclusion, HIF-1α and cAMP regulate MIF in primary tubular cells and cyst-lining epithelial cells, and MIF promotes cyst growth in the absence of macrophages. In line with these findings, the MIF inhibitor ISO-1 attenuates HIF-1α- and cAMP-dependent in vitro cyst enlargement. KEY MESSAGES: • MIF is upregulated in cyst-lining cells in a polycystic kidney disease mouse model. • MIF upregulation is mediated by hypoxia-inducible transcription factor (HIF) 1α. • ABCA1, transport protein for MIF, is also regulated by HIF-1α in vitro and in vivo. • MIF is additionally regulated by cAMP, a strong promotor of cyst growth. • MIF-inhibitor ISO-1 reduces HIF-1α- and cAMP-dependent cyst growth.
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