• 検索結果がありません。

NUPR1 acts as a pro-survival factor in human bone marrow-derived mesenchymal stem cells and is induced by the hypoxia mimetic reagent deferoxamine

N/A
N/A
Protected

Academic year: 2021

シェア "NUPR1 acts as a pro-survival factor in human bone marrow-derived mesenchymal stem cells and is induced by the hypoxia mimetic reagent deferoxamine"

Copied!
20
0
0

読み込み中.... (全文を見る)

全文

(1)

ÒËÐÎï ¿½¬ ¿ ¿ °®±ó «®ª ª¿´ º¿½¬±® ² ¸«³¿² ¾±²»

³¿®®±©ó¼»® ª»¼ ³» »²½¸§³¿´ ¬»³ ½»´´ ¿²¼

²¼«½»¼

¾§ ¬¸» ¸§°±¨ ¿ ³ ³»¬ ½ ®»¿¹»²¬ ¼»º»®±¨¿³ ²»

(2)

É» ¬»®² ¾´±¬ ¿²¿´§

ÎÒß

ÍßÙÛ

Ѩ§¹»² ½±² «³°¬ ±² ®¿¬»

ÑÝÎ

(3)

ï ÓÍÝ Ü»º»®±¨¿³ ²» øÜÚÑ÷ ïî ÜÚÑ ßÌÐ ÜÚÑ «° ¬®»¿³ ÒËÐÎï ÛÙÔÒ ÓÍÝ ÜÚÑ «° ¬®»¿³ ÒËÐÎï ÒËÐÎï ÜÚÑ ÒËÐÎï ¬¿«®± °±® ²» ÒËÐÎï ÜÚÑ ÒËÐÎï ÓÍÝ ÓÍÝ øÞÓÍÝ÷ ÞÓÍÝ ÞÓÍÝ ïóéû ÞÓÍÝ îïû Å Ã ÓÍÝ Å Ã

(4)

î ¼»º»®±¨¿³ ²» øÜÚÑ÷ Å Ã ÜÚÑ °®±´§´óì ¸§¼®±¨§´¿ » Ø×Úï ÜÚÑ ÓÍÝ ÜÚÑ ÜÚÑ Å Ã ÓÍÝ ÜÚÑ ÓÍÝ Å Ã Å Ã ÜÚÑ ÓÍÝ Å Ã ÜÚÑ ÜÚÑ ÓÍÝ ÓÍÝ ÜÚÑ Å Ã ²«½´»¿® °®±¬» ² ï ÒËÐÎï ø °è÷ °ëí Å Ã ÒËÐÎï ÒËÐÎï ÜÚÑ ÓÍÝ ÜÚÑ ÒËÐÎï ÓÍÝ ÞÓÍÝ Þ±²» ³¿®®±© ½»´´ øÔ±²¦¿ô Þ¿ »´ô Í© ¬¦»®´¿²¼ ÜÓÛÓ ÞÓÍÝ í è ÞÓÍÝ ÝÜìëøó÷ô ÝÜïï¾øó÷ô ÝÜçðøõ÷ô ÝÜéíøõ÷ô ÝÜïðëøõ÷

(5)

í çê ©»´´ ïôððð ñ©»´´ ÓÍÝ ÜÚÑ ×²½«½§¬» ØÜ ³¿¹ ²¹ § ¬»³ øÛ »² Þ ±Í½ »²½»÷ ÜÚÑ Ì±µ§±ô Ö¿°¿² ÎÒß çê ©»´´ íôððð ñ©»´´ í ê øÌ¸»®³± Ú ¸»® ͽ »²¬ º ½÷ Ý¿ °¿ »óí ß ¿§ Õ ¬øÐ®±³»¹¿÷ Ý¿ °¿ »í ²ãê Ì® °´ ½¿¬»

É» ¬»®² ¾´±¬ ¿²¿´§

É» ¬»®² ¾´±¬ Å Ã êîòë ³Ó Ì® óØÝ´ø°Øêòè ìûÍÜÍ îðð ³Ó ïîû 󿽬 ² øÍ ¹³¿÷ °êî ø¿¾½¿³÷ ÔÝí øÔ º» Ì»½¸²±´±¹§÷ ÒËÐÎï øÐ®±¬» ² ݸ ½¿¹± ×Ô÷

ÎÒß

ÎÒß ÌÎצ±´ λ¿¹»²¬ øÔ º» Ì»½¸²±´±¹§÷ ÍÊ Ì±¬¿´ ÎÒß × ±´¿¬ ±² ͧ ¬»³ øÐ®±³»¹¿÷ ÎÒß ÒÜóïððð °»½¬®±°¸±¬±³»¬»® øÒ¿²±Ü®±° Ì»½¸²±´±¹ » ô É ´³ ²¹¬±²ô ÜÛ÷ Û¨°»® ±² ͧ ¬»³ øÞ ±óο¼ Ô¿¾±®¿¬±® » ô Ø»®½«´» ô Ýß÷

ÍßÙÛ

×±² ß³°´ »¯ Ì®¿² ½® °¬±³» Ø«³¿² Ù»²» Û¨°®» ±² Õ ¬ øÔ º» Ì»½¸²±´±¹ » ÷ ×±² Ю±¬±² ×±² Ð× ×Ý îðð Õ ¬ øÔ º» Ì»½¸²±´±¹ » ÷ ×±² Ð× Ý¸ ° Õ ¬ ªî ÞÝ ×±² Ю±¬±² ²»¨¬ó¹»²»®¿¬ ±² »¯«»²½»® ÍßÙÛ ×²¹»²« ¬§ п¬¸©¿§ ß²¿´§ ø×Ðß÷

(6)

ì

Ѩ§¹»² ½±² «³°¬ ±² ®¿¬» øÑÝÎ÷

ÑÝÎ Í»¿¸±® » Þ ± ½ »²½» ÈÚçê Û¨¬®¿½»´´«´¿® Ú´«¨ ß²¿´§¦»® ÈÚçê ³ ½®±°´¿¬» øÍ»¿¸±® » Þ ± ½ »²½» ÷ íôððð ñ©»´´ îì ÈÚ ß ¿§ Ó»¼ «³ øÍ»¿¸±® » Þ ± ½ »²½» ÷ îë ³Ó øÍ ¹³¿óß´¼® ½¸÷ ÑÝÎ í ë óß´¼® ½¸÷ íðð ²Ó ½¿®¾±²§´½§¿² ¼»ó°ó¬® º´«±®±³»¬¸±¨§°¸»²§´¸§¼®¿¦±²» øÚÝÝÐå Í ¹³¿óß´¼® ½¸÷ ®±¬»²±²» øÓÐ Þ ±³»¼ ½¿´ ÷ Í»¿¸±® » Þ ± ½ »²½» ² ¬®«½¬ ±² ÑÝÎ ÓÍÝ ìû Ѱ¿´ Ó«´¬ °´»¨ ׳³«²±¸ ¬±½¸»³ ¬®§ Õ ¬ øÐ»®µ ² Û´³»®ô Ò±®©¿´µô ÝÌ÷ Ú Ì Ì ° ðòðë

(7)

ë ÜÚÑ ßÌÐ ÜÚÑ ÜÚÑ ïî ìè ÜÚÑ ÜÚÑ ÜÚÑ ìè Åïîà ÜÚÑ ëð ïî øÚ ¹òïß÷ ßÌÐ ïðð ßÌÐ øÚ ¹òïÞ÷ ßÌÐ ÑÝÎ ±¨§¹»² ½±² «³°¬ ±² ®¿¬» ¾¿ ¿´ ®» ° ®¿¬ ±² ³¿¨ ³«³ ®» ° ®¿¬ ±² ïð ïðð íðð øÚ ¹ò ïÝ÷ Ú ¹ ï ÞÓÍÝ ÜÚÑ ßÌÐ ßòÜÚÑ ÓÍÝ ÜÚÑ ïî ø ÷ ìè ø ÷ ÜÚÑ

(8)

ê

Þò ßÌÐ ÜÚÑ

ÜÚÑ ïî ßÌÐ ßÌÐ ö° ä ðòðëò

(9)

é ÜÚÑ ÓÍÝ ÜÚÑ ëð ïî ÎÒß ×Ðß Ù´§½±´§ Ù´«½±²»±¹»²» ÊÛÙÚ øÚ ¹òîß÷ Ù´§½±´§ ¹´«½± » ê °¸± °¸¿¬» ±³»®¿ »ô ê󰸱 °¸±º®«½¬±µ ²¿ »ô º®«½¬± »ó¾ °¸± °¸¿¬» ¿´¼±´¿ »ô ¬® ± »ó°¸± °¸¿¬» ±³»®¿ »ô ¹´§½»®¿´¼»¸§¼»óí󰸱 °¸¿¬» ¼»¸§¼®±¹»²¿ »ô °¸± °¸±¹´§½»®¿¬» µ ²¿ »ô °¸± °¸±¹´§½»®¿¬» ³«¬¿ »ô °¸± °¸±°§®«ª¿¬» ¸§¼®¿¬¿ » øÚ ¹òîÞ÷ Ø×Úï ÙÔËÌ ÔÜØ ÊÛÙÚ ÜÚÑ øÚ ¹òîÝ÷ ß½¬ ª¿¬»¼ ײ¸ ¾ ¬ ˰ ¬®»¿³ Ü»º»®±¨¿³ ²» ß½¬ ª¿¬» ÛÐßÍï ÐÜÙÚ ÒËÐÎï ˰ ¬®»¿³ ÛÙÔÒ Ø§°±¨ ¿ó ²¼«½ ¾´» º¿½¬±® °®±´§´ ¸§¼®±¨§´¿ » ½«®½«³ ² øÚ ¹òîÜ÷ Ú ¹ î ÜÚÑ ßò ×Ðß

(10)

è Þò ¹´§½±´§ °¿¬¸©¿§

(11)

ç Üò ˰ ¬®»¿³ ®»¹«´¿¬±® ë ë ®»¹«´¿¬±® ÜÚÑ ÒËÐÎï ÜÚÑ í ìè ÓÍÝ ÒËÐÎï Åïîà ÒËÐÎï ÜÚÑ ÜÚÑ ÔÝíó °êî ½¸´±®±¯« ²»øÝÏ÷ ïê ÜÚÑ ÔÝíó êî øÚ ¹òíß÷ ÜÚÑ ïð Ó ÝÏ ÔÝí °«²½¬¿ ÜÚÑ øÚ ¹òíÞ÷ ÜÚÑ ìè ÒËÐÎï ÜÚÑ øÚ ¹òíÝ÷ ÜÚÑ ÒËÐÎï ÒËÐÎï øÚ ¹òíÜ÷ ØÞÍÍ î ÒËÐÎï øÚ ¹òíÛ÷

(12)

ïð Ú ¹ í ÜÚÑ ÒËÐÎï

ß ÜÚÑ

ݸ´±®±¯« ²» øÝÏ÷ ïê

(13)

ïï Ý ÜÚÑ ÒËÐÎï

Ü ÒËÐÎï

(14)

ïî ÒËÐÎï ÓÍÝ Ü®«¹ ®» ¬¿²½» ÓÍÝ ÒËÐÎï ÎÒß ÒËÐÎï ÔÝíó øÚ ¹òìß÷ ÒËÐÎï ÜÚÑ øÚ ¹òìÞ÷ ÒËÐÎï ¼®«¹ ®» ¬¿²½» ¬¿«®± °±® ²» ÒËÐÎï ¬¿«®± °±® ²» Ý¿ °¿ »í øÚ ¹òìÝ÷ Ú ¹ ì ÒËÐÎï ß ÎÒß ÒËÐÎï ÓÍÝ

(15)

ïí Þ ÒËÐÎï ÓÍÝ ×²½«½§¬» î ø²ãê÷ Þ ÒËÐÎï ͬ¿«®± °±® ²» ¬¿«®± °±® ²» ê Ý¿ °í Ý¿ °í öö ÝÑÒÌÎÑÔýï ° ä ðòðï

(16)

ïì ÓÍÝ ÓÍÝ Å Ã ÜÚÑ Å Ã ìè ÜÚÑ ïî ßÌÐ ÑÝÎ ìè ÓÍÝ ÜÚÑ ÐÜØ Ù´§½±´§ ê Ч®«ª¿¬» ë ÊÛÙÚ ïî «° ¬®»¿³ ®»¹«´¿¬±® ÒËÐÎï ÛÙÔÒ ÛÙÔÒ «° ¬®»¿³ ®»¹«´¿¬±® ÜÚÑ Åïëà Åïêà Åïëà «° ¬®»¿³ ®»¹«´¿¬±® ÒËÐÎï ìè Åïîà ÒËÐÎï ÒËÐÎï Åïíà °ëí ÜÚÑ ÓÍÝ ÜÚÑ ÝÏ ÔÝíó °êî ÒËÐÎï ÒËÐÎï ÜÚÑ Åïéà ÒרíÌí ÜÚÑ

(17)

ïë °êîñÍÏÍÌÓï Å Ã ÜÚÑ Å Ã ÒËÐÎï Å Ã ÒËÐÎï ÎÒß ÓÍÝ ÒËÐÎï ÒËÐÎï Å Ã ÒËÐÎï ÔÝíó ßëìç ÒËÐÎï ÒËÐÎï Å Ã ÒËÐÎï ÓÍÝ ø¼¿¬¿ ²±¬ ¸±©²÷ ÓÍÝ ÒËÐÎï ÒËÐÎï ¬¿«®± °±® ²» ÒËÐÎï ÒËÐÎï Å Ã ¹»³½ ¬¿¾ ²» ÒËÐÎïñÎÛÔÞñ×ÛÎí «®ª ª¿´ °¿¬¸©¿§ ÝÜÕÒïßñ°îï ¼±¨±®«¾ ½ ² Å Ã °îï ø¼¿¬¿ ²±¬ ¸±©²÷ ÒËÐÎï Å Ã ÓÍÝ ÒËÐÎï ÓÍÝ ïî ÜÚÑ ÜÚÑ ÒËÐÎï ÓÍÝ ÓÍÝ

(18)

ïê ÞÓÍÝ ÜÚÑ ÒËÐÎï ÞÓÍÝ Ö±«®²¿´ ±º Ý´ ² ½¿´ Þ ±½¸»³ ¬®§ ¿²¼ Ò«¬® ¬ ±² ÒËÐÎï ¿½¬ ¿ ¿ °®±ó «®ª ª¿´ º¿½¬±® ² ¸«³¿² ¾±²» ³¿®®±©ó¼»® ª»¼ ³» »²½¸§³¿´ ¬»³ ½»´´ ¿²¼ ²¼«½»¼ ¾§ ¬¸» ¸§°±¨ ¿ ³ ³»¬ ½ ®»¿¹»²¬ ¼»º»®±¨¿³ ²» Õ¿¦«¸ ¬± Ó¿¬ «²¿¹¿ô Õ± ½¸ Ú«¶ ¿©¿ô Ì¿®± Ì¿µ¿³ ô Ù«¦»´ Þ«®¹¿²±ª¿ô Ò¿²¿³ Í¿ ¿ ô ̱ ¸ ¸ µ± Ó¿¬ «³±¬±ô Ò¿±µ Ç¿³¿³±¬±ô × ¿± Í¿µ¿ ¼¿

(19)

ïé

1 Dos Santos F, Andrade PZ, Boura JS, Abecasis MM, da Silva CL, Cabral JM. Ex vivo expansion of human mesenchymal stem cells: a more effective cell proliferation kinetics and metabolism under hypoxia. J Cell Physiol. 2010 Apr;223: 27-35.

2 Hoch AI, Leach JK. Concise review: optimizing expansion of bone marrow mesenchymal stem/stromal cells for clinical applications. Stem Cells Transl Med. 2014 May;3: 643-52.

3 Sugrue T, Lowndes NF, Ceredig R. Hypoxia enhances the radioresistance of mouse mesenchymal stromal cells. Stem Cells. 2014 Aug;32: 2188-200.

4 Beegle J, Lakatos K, Kalomoiris S, et al. Hypoxic preconditioning of mesenchymal stromal cells induces metabolic changes, enhances survival, and promotes cell retention in vivo. Stem Cells. 2015 Jun;33: 1818-28.

5 Rosova I, Dao M, Capoccia B, Link D, Nolta JA. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells. 2008 Aug;26: 2173-82.

6 Oses C, Olivares B, Ezquer M, et al. Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy. PLoS One. 2017;12: e0178011.

7 Nouri F, Salehinejad P, Nematollahi-Mahani SN, Kamarul T, Zarrindast MR, Sharifi AM. Deferoxamine Preconditioning of Neural-Like Cells Derived from Human Wharton's Jelly Mesenchymal Stem Cells as a Strategy to Promote Their Tolerance and Therapeutic Potential: An In Vitro Study. Cell Mol Neurobiol. 2016 Jul;36: 689-700.

8 Cheng XW, Kuzuya M, Kim W, et al. Exercise training stimulates ischemia-induced neovascularization via phosphatidylinositol 3-kinase/Akt-dependent hypoxia-induced factor-1 alpha reactivation in mice of advanced age. Circulation. 20factor-10 Aug factor-17;factor-122: 707-factor-16.

9 Najafi R, Sharifi AM. Deferoxamine preconditioning potentiates mesenchymal stem cell homing in vitro and in streptozotocin-diabetic rats. Expert Opin Biol Ther. 2013 Jul;13: 959-72.

10 Qin HH, Filippi C, Sun S, Lehec S, Dhawan A, Hughes RD. Hypoxic preconditioning potentiates the trophic effects of mesenchymal stem cells on co-cultured human primary hepatocytes. Stem cell research & therapy. 2015 Dec 1;6: 237.

11 Chu K, Jung KH, Kim SJ, et al. Transplantation of human neural stem cells protect against ischemia in a preventive mode via hypoxia-inducible factor-1alpha stabilization in

(20)

ïè the host brain. Brain Res. 2008 May 1;1207: 182-92.

12 Fujisawa K, Takami T, Okada S, et al. Analysis of Metabolomic Changes in Mesenchymal Stem Cells on Treatment with Desferrioxamine as a Hypoxia Mimetic Compared with Hypoxic Conditions. Stem Cells. 2018 Aug;36: 1226-36.

13 Hamidi T, Cano CE, Grasso D, et al. Nupr1-aurora kinase A pathway provides protection against metabolic stress-mediated autophagic-associated cell death. Clin Cancer Res. 2012 Oct 1;18: 5234-46.

14 Fujisawa K, Hara K, Takami T, et al. Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells. Stem cell research & therapy. 2018 Apr 6;9: 93.

15 Jiao Y, Wilkinson Jt, Christine Pietsch E, et al. Iron chelation in the biological activity of curcumin. Free Radic Biol Med. 2006 Apr 1;40: 1152-60.

16 Chin D, Huebbe P, Frank J, Rimbach G, Pallauf K. Curcumin may impair iron status when fed to mice for six months. Redox Biol. 2014;2: 563-9.

17 Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med. 2013 May 9;368: 1845-6.

18 Inoue H, Hanawa N, Katsumata SI, Katsumata-Tsuboi R, Takahashi N, Uehara M. Iron deficiency induces autophagy and activates Nrf2 signal through modulating p62/SQSTM. Biomed Res. 2017;38: 343-50.

19 Zheng Q, Zhao Y, Guo J, et al. Iron overload promotes mitochondrial fragmentation in mesenchymal stromal cells from myelodysplastic syndrome patients through activation of the AMPK/MFF/Drp1 pathway. Cell Death Dis. 2018 May 1;9: 515.

20 Grasso D, Garcia MN, Hamidi T, et al. Genetic inactivation of the pancreatitis-inducible gene Nupr1 impairs PanIN formation by modulating Kras(G12D)-induced senescence. Cell Death Differ. 2014 Oct;21: 1633-41.

21 Mu Y, Yan X, Li D, et al. NUPR1 maintains autolysosomal efflux by activating SNAP25 transcription in cancer cells. Autophagy. 2018;14: 654-70.

22 Malicet C, Giroux V, Vasseur S, Dagorn JC, Neira JL, Iovanna JL. Regulation of apoptosis by the p8/prothymosin alpha complex. Proc Natl Acad Sci U S A. 2006 Feb 21;103: 2671-6.

23 Vincent AJ, Ren S, Harris LG, et al. Cytoplasmic translocation of p21 mediates NUPR1-induced chemoresistance: NUPR1 and p21 in chemoresistance. FEBS Lett. 2012 Sep 21;586: 3429-34.

24 Narzt MS, Nagelreiter IM, Oskolkova O, et al. A novel role for NUPR1 in the keratinocyte stress response to UV oxidized phospholipids. Redox Biol. 2018 Nov 13;20: 467-82.

参照

関連したドキュメント

PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in

Northern blot analysis using 5’ portion of the chicken DDB1 cDNA as a probe detected a single transcript of ~ 4.3 kb in chicken DT40 cells as well as in human HeLa cells

Ability of HBx to overcome H-RAS V12 -induced senescence in BJ cells immortalized by hTERT Seeing as HBx did not exhibit the ability to immortalize primary human fibroblasts or

We investigated whether HSCs activated by AngII in cancerous stromal tissues released SDF-1 into collagen-rich ICC tissues and hypothesized that the AngII/AngII type 1

Accordingly, our results showed that kahweol acetate and cafestol inhibited the proliferation and migration of both ACHN and Caki-1 cells, with their synergistic effects apparent

Character- ization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. IGFBP-4 is an inhibitor of canonical Wnt signalling

To determine the promoter activities of 5 ′ -flanking region of the human Pim-3 gene, we subcloned various deleted 5 ′ -flanking regions of the human Pim-3 gene into a

After the cell divisions of the immediate sister cell and its daughter cells (figure 1a, the green cells), the gametophore apical stem cell divided again to produce a new