FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2767950681> ?p ?o ?g. }

• W2767950681 endingPage "284" @default.
• W2767950681 startingPage "271" @default.
• W2767950681 abstract "The hypoxic response is a stress response triggered by low oxygen tension. Hypoxia-inducible factors (HIFs) play a prominent role in the pathobiology of hypoxia-associated conditions, including pulmonary hypertension (PH) and polycythemia. The c-Jun N-terminal protein kinase (JNK), a stress-activated protein kinase that consists of two ubiquitously expressed isoforms, JNK1 and JNK2, and a tissue-specific isoform, JNK3, has been shown to be activated by hypoxia. However, the physiological role of JNK1 and JNK2 in the hypoxic response remains elusive. Here, using genetic knockout cells and/or mice, we show that JNK2, but not JNK1, up-regulates the expression of HIF-1α and HIF-2α and contributes to hypoxia-induced PH and polycythemia. Knockout or silencing of JNK2, but not JNK1, prevented the accumulation of HIF-1α in hypoxia-treated cells. Loss of JNK2 resulted in a decrease in HIF-1α and HIF-2α mRNA levels under resting conditions and in response to hypoxia. Consequently, hypoxia-treated Jnk2−/− mice had reduced erythropoiesis and were less prone to polycythemia because of decreased expression of the HIF target gene erythropoietin (Epo). Jnk2−/− mice were also protected from hypoxia-induced PH, as indicated by lower right ventricular systolic pressure, a process that depends on HIF. Taken together, our results suggest that JNK2 is a positive regulator of HIFs and therefore may contribute to HIF-dependent pathologies. The hypoxic response is a stress response triggered by low oxygen tension. Hypoxia-inducible factors (HIFs) play a prominent role in the pathobiology of hypoxia-associated conditions, including pulmonary hypertension (PH) and polycythemia. The c-Jun N-terminal protein kinase (JNK), a stress-activated protein kinase that consists of two ubiquitously expressed isoforms, JNK1 and JNK2, and a tissue-specific isoform, JNK3, has been shown to be activated by hypoxia. However, the physiological role of JNK1 and JNK2 in the hypoxic response remains elusive. Here, using genetic knockout cells and/or mice, we show that JNK2, but not JNK1, up-regulates the expression of HIF-1α and HIF-2α and contributes to hypoxia-induced PH and polycythemia. Knockout or silencing of JNK2, but not JNK1, prevented the accumulation of HIF-1α in hypoxia-treated cells. Loss of JNK2 resulted in a decrease in HIF-1α and HIF-2α mRNA levels under resting conditions and in response to hypoxia. Consequently, hypoxia-treated Jnk2−/− mice had reduced erythropoiesis and were less prone to polycythemia because of decreased expression of the HIF target gene erythropoietin (Epo). Jnk2−/− mice were also protected from hypoxia-induced PH, as indicated by lower right ventricular systolic pressure, a process that depends on HIF. Taken together, our results suggest that JNK2 is a positive regulator of HIFs and therefore may contribute to HIF-dependent pathologies." @default.
• W2767950681 created "2017-11-17" @default.
• W2767950681 creator A5003416748 @default.
• W2767950681 creator A5012708220 @default.
• W2767950681 creator A5015940297 @default.
• W2767950681 creator A5024741363 @default.
• W2767950681 creator A5039614597 @default.
• W2767950681 creator A5042890673 @default.
• W2767950681 creator A5043224088 @default.
• W2767950681 creator A5046518034 @default.
• W2767950681 creator A5067331026 @default.
• W2767950681 creator A5081897750 @default.
• W2767950681 creator A5084997419 @default.
• W2767950681 creator A5088170766 @default.
• W2767950681 creator A5089270049 @default.
• W2767950681 creator A5089320354 @default.
• W2767950681 date "2018-01-01" @default.
• W2767950681 modified "2023-09-26" @default.
• W2767950681 title "JNK2 up-regulates hypoxia-inducible factors and contributes to hypoxia-induced erythropoiesis and pulmonary hypertension" @default.
• W2767950681 cites W1545825939 @default.
• W2767950681 cites W1554617702 @default.
• W2767950681 cites W1749022239 @default.
• W2767950681 cites W1965286369 @default.
• W2767950681 cites W1972145919 @default.
• W2767950681 cites W1974896352 @default.
• W2767950681 cites W1975124019 @default.
• W2767950681 cites W1980111004 @default.
• W2767950681 cites W1981104972 @default.
• W2767950681 cites W1989188574 @default.
• W2767950681 cites W1991346678 @default.
• W2767950681 cites W1997031088 @default.
• W2767950681 cites W2003879854 @default.
• W2767950681 cites W2004294204 @default.
• W2767950681 cites W2005539293 @default.
• W2767950681 cites W2010422443 @default.
• W2767950681 cites W2011760895 @default.
• W2767950681 cites W2013211910 @default.
• W2767950681 cites W2019148350 @default.
• W2767950681 cites W2020277250 @default.
• W2767950681 cites W2022632625 @default.
• W2767950681 cites W2031920769 @default.
• W2767950681 cites W2035192492 @default.
• W2767950681 cites W2038300452 @default.
• W2767950681 cites W2038711570 @default.
• W2767950681 cites W2040532363 @default.
• W2767950681 cites W2044257922 @default.
• W2767950681 cites W2045087843 @default.
• W2767950681 cites W2074971666 @default.
• W2767950681 cites W2076153728 @default.
• W2767950681 cites W2076485183 @default.
• W2767950681 cites W2077880395 @default.
• W2767950681 cites W2080741365 @default.
• W2767950681 cites W2085423203 @default.
• W2767950681 cites W2085609942 @default.
• W2767950681 cites W2086812941 @default.
• W2767950681 cites W2090739772 @default.
• W2767950681 cites W2091709423 @default.
• W2767950681 cites W2092762008 @default.
• W2767950681 cites W2105846857 @default.
• W2767950681 cites W2107183424 @default.
• W2767950681 cites W2109709409 @default.
• W2767950681 cites W2113070607 @default.
• W2767950681 cites W2116240300 @default.
• W2767950681 cites W2125475136 @default.
• W2767950681 cites W2127154601 @default.
• W2767950681 cites W2128781685 @default.
• W2767950681 cites W2131456001 @default.
• W2767950681 cites W2131676053 @default.
• W2767950681 cites W2135034560 @default.
• W2767950681 cites W21419008 @default.
• W2767950681 cites W2144795074 @default.
• W2767950681 cites W2147286587 @default.
• W2767950681 cites W2149751735 @default.
• W2767950681 cites W2153871240 @default.
• W2767950681 cites W2160252424 @default.
• W2767950681 cites W2162484465 @default.
• W2767950681 cites W2165946847 @default.
• W2767950681 cites W2168306631 @default.
• W2767950681 cites W2184465182 @default.
• W2767950681 cites W2196899564 @default.
• W2767950681 cites W2512508925 @default.
• W2767950681 cites W4229667826 @default.
• W2767950681 cites W4243541841 @default.
• W2767950681 cites W3142959081 @default.
• W2767950681 doi "https://doi.org/10.1074/jbc.ra117.000440" @default.
• W2767950681 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5766905" @default.
• W2767950681 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29118187" @default.
• W2767950681 hasPublicationYear "2018" @default.
• W2767950681 type Work @default.
• W2767950681 sameAs 2767950681 @default.
• W2767950681 citedByCount "14" @default.
• W2767950681 countsByYear W27679506812018 @default.
• W2767950681 countsByYear W27679506812019 @default.
• W2767950681 countsByYear W27679506812020 @default.
• W2767950681 countsByYear W27679506812021 @default.
• W2767950681 countsByYear W27679506812022 @default.
• W2767950681 crossrefType "journal-article" @default.
• W2767950681 hasAuthorship W2767950681A5003416748 @default.

• next