ABSTRACT
Ischemic stroke, gravely affecting human health with its increasing incidence rate , is a common disease of old age . JAK/STAT way , a recently discovered signaling pathway , is not only widely involved in processes of cell growth ,differentiation, and apoptosis ,but also closely related to the pathophysiology of stroke.However,the pathway function and mechanism in ische-mic cerebral stroke has not yet been fully elucidated .We will review the role and mechanism of JAK/STAT signal transduction pathway in ischemic stroke ,and scientifically draw network chart between various related signal molecules in the process of ische-mic stroke neuropathy combining both domestic and foreign re-search reported in this paper , in order to better understand the pathological mechanism process of brain stroke , find new drugs for the treatment of cerebral ischemic diseases ,then provide more systematic scientific literature support .
ABSTRACT
AIM: To investigate the effect of activation of JAK/STAT signaling pathway on the transdifferentiation induced by high concentration of glucose in renal proximal tubular epithelial cells(HKCs).METHODS: Cultured HKCs cells were divided into four groups: low glucose group(LG),high glucose group(HG),high mannitol group(LG+M),and HG+AG490 group(AG).Immunoprecipitation and Western blotting analysis were used to determine the expression of tryosine phosphorylated Janus kinase 2(p-JAK2).The protein expressions of STAT1,STAT3,p-STAT1 and p-STAT3 and expressions of ?-SMA,E-cadherin were observed by Western blotting.The contents of TGF-?1 and type I collagen in the supernatants of the cultured HKCs were detected by enzyme-linked immunoadsorbent assay(ELISA).TGF-?1 mRNA were measured by reverse transcription and polymerase chain reaction(RT-PCR).RESULTS: Compared with low glucose control group,the expression of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA was significantly increased in HG group at different stimulated time from 6 h to 72 h.Meanwhile,the contents of TGF-?1 and collagen I in the supernatants and the expression of ?-SMA were increased,the expression of E-cadherin were decreased.The expression of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA and the levels of TGF-?1,collagen I in the supernatants in HG+AG490 group were obviously lower than those in HG group.The expressions of ?-SMA and E-cadherin were also decreased in HG+AG490 group.CONCLUSION: Activation of JAK/STAT signaling pathway may be involved in the high glucose-induced transdifferentiation and overproduction of TGF?1 and ECM proteins in HKCs.