Role of angiotensin II and JAK2 signal pathway in transdifferentation of renal tubular cells in mice after acute ischemic followed by reperfusion.
- Author:
Tang JIANG
1
;
Qing-song ZHOU
;
Lei PI
;
Bin HUANG
Author Information
- Publication Type:Journal Article
- MeSH: Actins; genetics; metabolism; Angiotensin II; administration & dosage; metabolism; pharmacology; Angiotensin II Type 1 Receptor Blockers; pharmacology; Animals; Cell Differentiation; drug effects; Cell Line; Dose-Response Relationship, Drug; Imidazoles; pharmacology; Janus Kinase 2; antagonists & inhibitors; Kidney Tubules; cytology; metabolism; Male; Pyridines; pharmacology; RNA, Messenger; metabolism; Rats; Rats, Wistar; Renin-Angiotensin System; Reperfusion Injury; metabolism; pathology; Signal Transduction; drug effects; Tyrphostins; pharmacology
- From: Chinese Journal of Pathology 2009;38(7):466-471
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSModels 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.
RESULTSAngII 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.
CONCLUSIONSTransdifferentiation 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.
