[Role of angiotensin II and JAK2 signal pathway in transdifferentation of renal tubular cells in mice after acute ischemic followed by reperfusion].
OBJECTIVE
To investigate the effect of angiotensin (Ang)II and its Janns-activated kinase-2 (JAK2) signal pathway in transdifferentiation of renal tubular cells under the challenge of acute ischemic reperfusion injury.


METHODS
Models of acute ischemic reperfusion injury were established and the level of local AngII, a key element of renin-angiotensin system (RAS), in kidney was measured using radioimmunity technique. The expression of alpha-smooth muscle actin (alpha-SMA), a phenotype of mesenchymal cells, was detected by RT-PCR and immunohistochemistry methods. Renal tubule cells (NRK-52E) were cultured with various concentration of AngII, followed by blocking of PD123319, AngII receptor 2 antagonist, and AG490, an inhibitor of JAK2 signal pathway.


RESULTS
AngII of kidney tissue increased immediately after acute ischemic-reperfusion injury, in time dependent fashion. Expression of alpha-SMA in renal tubule cells was found at 48 hours after ischemic-reperfusion injury and in NRK-52E cells treated by high concentration of AngII and was dose and time dependent. The peak of alpha-SMA expression was seen after 30 minute treatment at the dose of 10(-9) mol/L, which was interrupted by both of PD123319 and AG490.


CONCLUSIONS
Transdifferentiation of renal tubular epithelial cells occurs under acute ischemic-reperfusion injury. Local renin-angiotensin system may play a role in the transdifferentiation of TEC through AT2 receptor and its JAK2 signal pathway.
Jiang
Tang
T
Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. jennyj@vip.163.com
Zhou
Qing-song
QS
Pi
Lei
L
Huang
Bin
B
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology
D000199:Actins; D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D053614:Janus Kinase 2; D011725:Pyridines; D012333:RNA, Messenger; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C498862:Acta2 protein, rat; C073402:PD 123319; C507927:Jak2 protein, rat