ELIZA

return kwic search for significantly out of >500 occurrences
583352 occurrences (No.14 in the rank) during 5 years in the PubMed. [cache]

271) Here, we report that Piezo1 is significantly upregulated in PAECs from patients with idiopathic PAH and animals with experimental pulmonary hypertension (PH) compared with normal controls.

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PMID:34669509 DOI:10.1152/ajpcell.00147.2021

2021 American journal of physiology. Cell physiology

* Endothelial upregulation of mechanosensitive channel Piezo1 in pulmonary hypertension.

- Piezo is a mechanosensitive cation channel responsible for stretch-mediated Ca²⁺ and Na⁺ influx in multiple types of cells. Little is known about the functional role of Piezo1 in the lung vasculature and its potential pathogenic role in pulmonary arterial hypertension (PAH). Pulmonary arterial endothelial cells (PAECs) are constantly under mechanic stretch and shear stress that are sufficient to activate Piezo channels. Here, we report that Piezo1 is significantly upregulated in PAECs from patients with idiopathic PAH and animals with experimental pulmonary hypertension (PH) compared with normal controls. Membrane stretch by decreasing extracellular osmotic pressure or by cyclic stretch (18% CS) increases Ca²⁺-dependent phosphorylation (p) of AKT and ERK, and subsequently upregulates expression of Notch ligands, Jagged1/2 (Jag-1 and Jag-2), and Delta like-4 (DLL4) in PAECs. siRNA-mediated downregulation of Piezo1 significantly inhibited the stretch-mediated pAKT increase and Jag-1 upregulation, whereas downregulation of AKT by siRNA markedly attenuated the stretch-mediated Jag-1 upregulation in human PAECs. Furthermore, the mRNA and protein expression level of Piezo1 in the isolated pulmonary artery, which mainly contains pulmonary arterial smooth muscle cells (PASMCs), from animals with severe PH was also significantly higher than that from control animals. Intraperitoneal injection of a Piezo1 channel blocker, GsMTx4, ameliorated experimental PH in mice. Taken together, our study suggests that membrane stretch-mediated Ca²⁺ influx through Piezo1 is an important trigger for pAKT-mediated upregulation of Jag-1 in PAECs. Upregulation of the mechanosensitive channel Piezo1 and the resultant increase in the Notch ligands (Jag-1/2 and DLL4) in PAECs may play a critical pathogenic role in the development of pulmonary vascular remodeling in PAH and PH.

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[frequency of next (right) word to significantly]

(1)44 higher	(17)6 with	(33)4 in	(49)2 faster
(2)35 increased	(18)5 and	(34)4 suppressed	(50)2 increases
(3)33 associated	(19)5 better	(35)3 (p	(51)2 influence
(4)25 reduced	(20)5 enhanced	(36)3 change	(52)2 inhibit
(5)20 lower	(21)5 enriched	(37)3 diminished	(53)2 larger
(6)19 decreased	(22)5 less	(38)3 increase	(54)2 lowered
(7)15 different	(23)5 related	(39)3 longer	(55)2 modified
(8)14 more	(24)4 null	(40)2 (P	(56)2 over
(9)13 greater	(25)4 altered	(41)2 affected	(57)2 positively
(10)12 improved	(26)4 between	(42)2 alleviated	(58)2 prolong
(11)11 correlated	(27)4 by	(43)2 alter	(59)2 reduce
(12)10 inhibited	(28)4 downregulated	(44)2 at	(60)2 reduces
(13)6 attenuated	(29)4 elevated	(45)2 changed	(61)2 reversed
(14)6 predicted	(30)4 impact	(46)2 declined
(15)6 to	(31)4 improve	(47)2 decreased,
(16)6 upregulated	(32)4 improves	(48)2 expanded

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--- WordNet output for significantly --- =>きわめて, 意味深く, 意味ありげに Overview of adv significantly The adv significantly has 3 senses (first 2 from tagged texts) 1. (6) significantly -- (in a statistically significant way; "the two groups differed significantly") 2. (3) significantly -- (in a significant manner; "our budget will be significantly affected by these new cuts") 3. importantly, significantly -- (in an important way or to an important degree; "more importantly, Weber held that the manifold meaning attached to the event by the social scientist could alter his definition of the concrete event itself") --- WordNet end ---