ライフサイエンスコーパス: PPAR-delta

1 PPAR delta likely mediates this antiapoptotic effect bec

2 PPAR-delta activation also reduced HTT-induced neurotoxi

3 PPAR-delta agonists are known to enhance fatty acid meta

4 PPAR-delta also has a relatively high expression in the

5 PPAR-delta overexpression in colonic epithelial cells pr

6 PPAR-delta promotes colonic tumorigenesis.

7 PPAR-delta+ NG2 cell numbers were significantly higher t

8 PPAR-delta+ oligodendrocyte numbers declined at 1 dpi an

9 e (P = 0.026), and 2.25 +/- 0.25 in 15-LOX-1-PPAR-delta-Gut mice (P = 0.0006).

10 ession in colonic epithelial cells (15-LOX-1-PPAR-delta-Gut mice) suppressed these effects: the numbe

11 MP-7, CCND1 (Cyclin D1), CX43 (Connexin 43), PPAR-delta, and ITF2 genes in OEAs with deregulated beta

12 ings indicate cyclin D1, MMP-7, connexin 43, PPAR-delta, and ITF-2, likely play important roles in th

13 ewal potential of these organoid bodies in a PPAR-delta-dependent manner.

14 Notably, HFD- and agonist-activated PPAR-delta signalling endow organoid-initiating capacity

15 oding other PPAR family members (PPAR alpha, PPAR delta, or NUC-1) were unchanged or decreased.

16 roliferator-activated receptor (PPAR)-alpha, PPAR-delta, PPAR-gamma, cd36/Fat, and Ucp2, which coinci

17 ator-activated receptors (PPARs; PPAR-alpha, PPAR-delta, and PPAR-gamma) comprise a family of nuclear

18 ceptor isoforms, PPAR gamma, PPAR alpha, and PPAR delta, encoded by different genes.

19 echanistic relationship between 15-LOX-1 and PPAR-delta was previously unknown.

20 phosphorylation, IL-6 promoter activity, and PPAR-delta mRNA and protein expression.

21 ivated receptors (PPAR-alpha, PPAR-gamma and PPAR-delta) exemplify this connection, regulating divers

22 ts that activate PPAR-alpha, PPAR-gamma, and PPAR-delta alone or in combination have the potential to

23 ceptors (PPARs), PPAR-alpha, PPAR-gamma, and PPAR-delta.

24 A-7 cells express this receptor, and another PPAR delta agonist, docosahexaenoic acid, mimics the eff

25 by sulindac sulfone but can be bound by both PPAR delta and PPAR gamma.

26 nking model to distinguish between confirmed PPAR-delta agonists and random molecules.

27 oligodendrocytes in uninjured spinal cords; PPAR-delta was also detected in NG2 cells (potential oli

28 on in skeletal muscle resulting in decreased PPAR-delta activation.

29 (i) 13-S-HODE binds to PPAR-delta, decreases PPAR-delta activation, and down-regulates PPAR-delta exp

30 We show that mice deficient in PPAR-delta (PPAR-delta(-/-)) develop a severe inflammatory response

31 isome proliferator-activated receptor delta (PPAR-delta) agonist, has emerged as a promising alternat

32 isome proliferator-activated receptor delta (PPAR-delta) interacts with HTT and that mutant HTT repre

33 isome proliferator-activated receptor delta (PPAR-delta) signature in intestinal stem cells and proge

34 isome proliferator-activated receptor delta (PPAR-delta)-fatty-acid oxidation (FAO) pathway for the m

35 isome proliferator-activated receptor-delta (PPAR-delta) and sequestered it in cytoplasm, repressing

36 isome proliferator-activated receptor-delta (PPAR-delta) is induced when macrophages engulf apoptotic

37 isome proliferator-activated receptor-delta (PPAR-delta) may have important roles in FAO.

38 isome proliferator-activated receptor-delta (PPAR-delta), which is implicated in bile acid homoeostas

39 isome proliferator-activated receptor-delta (PPAR-delta).

40 isome proliferator-activated receptor-delta (PPAR-delta; also known as PPAR-beta) is expressed at hig

41 iating capacity to progenitors, and enforced PPAR-delta signalling permits these progenitors to form

42 played by PPAR nuclear receptors, especially PPAR-delta (Lee et al.), in the modulation of inflammato

43 A large proportion of NG2 cells expressed PPAR-delta after SCI, especially along lesion borders.

44 such that >20% of oligodendrocytes expressed PPAR-delta after SCI compared with approximately 10% in

45 ignificantly greater in mice nullizygous for PPAR-delta.

46 These studies revealed a role for PPAR-delta in DC in limiting Th cell priming during EAE.

47 onists were found to be highly selective for PPAR-delta and are structurally different than agonists

48 L >> LDL > HDL), PPAR isoform (PPAR alpha >> PPAR delta > PPAR gamma), and among fatty acid-releasing

49 resultant induction of apoptosis; and (iii) PPAR-delta is an important signaling receptor for 13-S-H

50 Our results implicate PPAR-delta in the regulation of intestinal adenoma growt

51 8 in wild-type littermates, 6.67 +/- 0.83 in PPAR-delta-Gut mice (P = 0.026), and 2.25 +/- 0.25 in 15

52 We show that mice deficient in PPAR-delta (PPAR-delta(-/-)) develop a severe inflammato

53 The most prominent increase in PPAR-delta+ oligodendrocytes was along lesion borders wh

54 cellular differentiation, the early rise in PPAR-delta+ NG2 cells followed by an increase in new PPA

55 Increased PPAR-delta transactivation ameliorated mitochondrial dys

56 These findings highlight how diet-modulated PPAR-delta activation alters not only the function of in

57 in liver and heart, in mouse skeletal muscle PPAR delta is severalfold more abundant than either PPAR

58 Thus, chronic myocardial PPAR-delta deficiency leads to lipotoxic cardiomyopathy.

59 Expression of dominant-negative PPAR-delta in the central nervous system of mice was suf

60 Expression of dominant-negative PPAR-delta specifically in the striatum of medium spiny

61 ta+ NG2 cells followed by an increase in new PPAR-delta+ oligodendrocytes suggests that this transcri

62 evious reports suggesting that activation of PPAR-delta potentiates colon polyp formation, here we sh

63 em cells), and pharmacological activation of PPAR-delta recapitulates the effects of a HFD on these c

64 se models of HD, pharmacologic activation of PPAR-delta using the agonist KD3010 improved motor funct

65 of mice with a synthetic ligand activator of PPAR-delta, GW0742, ameliorates experimental autoimmune

66 sion of these T helper subsets in the CNS of PPAR-delta(-/-) mice occurred as a result of a constella

67 However, the cell-specific contribution of PPAR-delta to the more severe CNS inflammatory response

68 ported that mice with a global deficiency of PPAR-delta develop an exacerbated course of experimental

69 Genetic deletion of PPAR-delta decreases expression of opsonins such as comp

70 ediated cardiomyocyte-restricted deletion of PPAR-delta in mice downregulates constitutive expression

71 We also show that the effect of PPAR-delta in inhibiting the production of IFN-gamma and

72 to examine the spatiotemporal expression of PPAR-delta in naive and injured spinal cords from adult

73 tudy, we studied the specific involvement of PPAR-delta in myeloid cells during EAE using mice that h

74 We have found that loss of PPAR-delta or inhibition of mitochondrial FAO induces lo

75 a critical step in NSAID down-regulation of PPAR-delta and the resultant induction of apoptosis; and

76 indings indicate that the down-regulation of PPAR-delta by 15-LOX-1 through 13-S-HODE is an apoptotic

77 We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-defi

78 Identification of 15-LOX-1 suppression of PPAR-delta to inhibit IL-6/STAT3 signaling-driven CAC tu

79 crease the affinity for the same peptides on PPAR delta and in one case on PPAR alpha.

80 liferator-activated receptor (PPAR)-alpha or PPAR-delta activation stimulates keratinocyte differenti

81 Overall PPAR-delta+ cell numbers declined at 1 day post injury (

82 Mechanistically, the PML-PPAR-delta-FAO pathway controls the asymmetric division

83 the tail group modifications imparted potent PPAR delta agonist activity, improvement of PPAR alpha a

84 those, 13 molecules were found as potential PPAR-delta agonist leads with EC(50) between 4-19 nM and

85 es PPAR-delta activation, and down-regulates PPAR-delta expression in colorectal cancer cells; (ii) t

86 rs to terminate inflammation, down-regulates PPAR-delta.

87 As previously reported, PPAR-delta was expressed by neurons and oligodendrocytes

88 racts with HTT and that mutant HTT represses PPAR-delta-mediated transactivation.

89 and sequestered it in cytoplasm, repressing PPAR-delta-mediated transactivation and mitochondrial fu

90 After spinal cord injury (SCI), PPAR-delta mRNA and protein were present early and incre

91 an and rodent myocytes, the highly selective PPAR delta agonist GW742 increased fatty acid oxidation

92 NSAIDs suppress PPAR-delta activity in colon cancer cells.

93 ed from individuals with HD, indicating that PPAR-delta activation may be beneficial in HD and relate

94 tes colon polyp formation, here we show that PPAR-delta attenuates colon carcinogenesis.

95 Together, our data show that PPAR-delta is a crucial determinant of constitutive myoc

96 We suggest that PPAR-delta is a potential therapeutic target in treating

97 Collectively, these findings suggest that PPAR-delta serves as an important molecular brake for th

98 We report the crystal structure of the PPAR delta ligand-binding domain (LBD) bound to either t

99 Exposure of Apc(min) mice to the PPAR-delta ligand GW501516 resulted in a significant inc

100 ect was on polyp size; mice treated with the PPAR-delta activator had a fivefold increase in the numb

101 (2) promotes survival of colonocytes through PPAR delta activation.

102 Thus, PPAR-delta has a pivotal role in orchestrating the timel

103 rent study shows that (i) 13-S-HODE binds to PPAR-delta, decreases PPAR-delta activation, and down-re

104 Subsequent docking to PPAR-delta structures was mainly evaluated by geometric

105 of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice.

106 d oligodendrocytes (bromodeoxyuridine+) were PPAR-delta+.

107 ic commitment of HSC daughter cells, whereas PPAR-delta activation increased asymmetric cell division

108 But it remains unclear whether PPAR-delta is required for maintaining basal myocardial

109 de disrupting the binding of TrkB 1-486 with PPAR-delta attenuated depression-like symptoms not only

110 Incubation of macrophages with PPAR-delta agonists was shown to inhibit foam cell forma

111 s of HSC maintenance, whereas treatment with PPAR-delta agonists improved HSC maintenance.