Renal Cyst Development in Mice with Conditional Inactivation of the von Hippel-Lindau Tumor Suppressor

Rapid alteration of gene expression in response to environmental changes is essential for normal development and behavior. The transcription factor hypoxia-inducible factor (HIF)-1 is well known to respond to alterations in oxygen availability. In nature, low oxygen environments are often found to contain high levels of hydrogen sulfide (H2S). Here, we show that Caenorhabditis elegans can have mutually exclusive responses to H2S and hypoxia, both involving HIF-1. Specifically, H2S results in HIF-1 activity throughout the hypodermis, whereas hypoxia causes HIF-1 activity in the gut as judged by a reporter for HIF-1 activity. C. elegans require hif-1 to survive in room air containing trace amounts of H2S. Exposure to H2S results in HIF-1 nuclear localization and transcription of HIF-1 targets. The effects of H2S on HIF-1 reporter activity are independent of von Hippel–Lindau tumor suppressor (VHL)-1, whereas VHL-1 is required for hypoxic regulation of HIF-1 reporter activity. Because H2S is naturally produced by animal cells, our results suggest that endogenous H2S may influence HIF-1 activity.

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A Novel Mutation in the Von Hippel-Lindau Tumor Suppressor Gene Identified in a Patient Presenting with Gestational Diabetes Mellitus

Endocrinology and Metabolism ◽

10.3803/enm.2013.28.4.320 ◽

2013 ◽

Vol 28 (4) ◽

pp. 320 ◽

Cited By ~ 2

Author(s):

Yun Hyi Ku ◽

Chang Ho Ahn ◽

Chan-Hyeon Jung ◽

Jie Eun Lee ◽

Lee-Kyung Kim ◽

...

Keyword(s):

Diabetes Mellitus ◽

Tumor Suppressor ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Tumor Suppressor Gene ◽

Novel Mutation ◽

Suppressor Gene ◽

Von Hippel Lindau

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Multiple Renal Cyst Development but Not Situs Abnormalities in Transgenic RNAi Mice against Inv::GFP Rescue Gene

PLoS ONE ◽

10.1371/journal.pone.0089652 ◽

2014 ◽

Vol 9 (2) ◽

pp. e89652

Author(s):

Yuki Kamijho ◽

Yayoi Shiozaki ◽

Eiki Sakurai ◽

Kazunori Hanaoka ◽

Daisuke Watanabe

Keyword(s):

Renal Cyst ◽

Cyst Development

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Obacunone Retards Renal Cyst Development in Autosomal Dominant Polycystic Kidney Disease by Activating NRF2

Antioxidants ◽

10.3390/antiox11010038 ◽

2021 ◽

Vol 11 (1) ◽

pp. 38

Author(s):

Zhiwei Qiu ◽

Jinzhao He ◽

Guangying Shao ◽

Jiaqi Hu ◽

Xiaowei Li ◽

...

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

Autosomal Dominant ◽

Renal Cyst ◽

Renal Diseases ◽

Therapeutic Drug ◽

Dependent Manner ◽

Polycystic Kidney ◽

Autosomal Dominant Polycystic Kidney ◽

Cyst Development

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterized by progressive enlargement of fluid-filled cysts derived from renal tubular epithelial cells, which has become the fourth leading cause of end-stage renal diseases. Currently, treatment options for ADPKD remain limited. The purpose of this study was to discover an effective therapeutic drug for ADPKD. With virtual screening, Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney-specific Pkd1 knockout mouse (PKD) model, we identified obacunone as a candidate compound for ADPKD drug discovery from a natural antioxidant compound library. In vitro experiments showed that obacunone significantly inhibited cyst formation and expansion of MDCK cysts and embryonic kidney cysts in a dose-dependent manner. In vivo, obacunone treatment significantly reduced the renal cyst development in PKD mice. Western blot and morphological analysis revealed that obacunone served as a NRF2 activator in ADPKD, which suppressed lipid peroxidation by up-regulating GPX4 and finally restrained excessive cell proliferation by down-regulating mTOR and MAPK signaling pathways. Experimental data demonstrated obacunone as an effective renal cyst inhibitor for ADPKD, indicating that obacunone might be developed into a therapeutic drug for ADPKD treatment.

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Renal complication of crizotinib: Crizotinib-associated complex renal cyst

The ASEAN Journal of Radiology ◽

10.46475/aseanjr.v21i1.67 ◽

2020 ◽

Vol 21 (1) ◽

pp. 44-56

Author(s):

Warissara Jutidamrongphan ◽

Pimporn Puttawibul

Keyword(s):

Renal Impairment ◽

Kinase Inhibitors ◽

Renal Cyst ◽

Renal Cysts ◽

Small Cell ◽

Small Cell Lung ◽

Anaplastic Lymphoma ◽

Renal Complication ◽

Alk Positive ◽

Cyst Development

Crizotinib is one of the first generations of tyrosine kinase inhibitors targeting anaplastic lymphoma kinase(ALK) and is recently found to be associated with the development of complex renal cysts with inconclusive explanation up to this time. Hereby, we discuss the hypothesis of Crizotinib-associated complex renal cyst development and coexisting renal impairment after initiation of the treatment in a 75-year-old man with ALK-positive non-small cell lung cancer whose complex renal cysts evolved after initiation and cessation of Crizotinib treatment. The coexistence as renal impairment persisted even after switching from Crizotinib to Ceritinib.

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