ABSTRACT
Ischemia-reperfusion injury (IRI) refers to the reperfusion injury caused by the recovery of blood supply of ischemic tissues or organs, which commonly occurs in organ transplantation and other surgical procedures. IRI may cause a series of severe clinical issues, such as delayed graft function, acute kidney injury, myocardial infarction, ischemic stroke and circulatory arrest, etc. These events yield high incidence and fatality. At present, no effective solution has been available. Transient receptor potential canonical 6 (TRPC6), a member of Ca2+ channel family, is highly expressed in multiple types of cells. It may adjust many physiological functions by regulating intracellular Ca2+ concentration, which has become an important target for developing therapeutic drugs for multiple diseases. In this article, research progresses on the introduction and function of TRPC6, the association between TRPC6 and IRI and the therapeutic prospect of TRPC6 targeted drugs in IRI were reviewed, aiming to provide novel insights into the prevention and treatment of IRI during organ transplantation
ABSTRACT
OBJECTIVE: To study the expression of transient receptor potential canonical-6(TRPC6)channels in endometrial cancer tissues and their role in regulating proliferation of endometrial cancer cells.METHODS: Thirty patients with endometrial cancer who were treated from January 2011 to June 2015 in Henan Provincial People's Hospital and Xuchang People's Hospital were chosen as the study group;the controls group consisted of 24 atypical hyperplasia patients and 28 uterus leiomyoma patients.Molecular biological techniques were used to examine the expression of TRPC6 channels in 30 endometrial cancer specimens,24 atypical hyperplasia specimens and 28 normal endometrial specimens.SKF96365(an inhibitor of TRPC6 channel)and siRNA interference(RNAi)targeting TRPC6 channel were used to block TRPC6 so as to explore the role of TRPC6 channels in regulating the proliferation of endometrial cancer cells by[3 H]thymidine incorporation and cell number.RESULTS: The expression levels of TRPC6 in endometrial cancer were notably elevated than those in the atypical hyperplasia endometrial and normal endometrial tissues. The expression levels of TRPC6 in endometrial cancer vs. the control:mRNA:(0.98±0.56)vs.(0.30±0.24 and0.23±0.13)(P<0.01):protein:(1.22±0.39)vs.(0.75±0.27 and 0.73±0.26)(P<0.01);The expression level of TRPC6in endometrial cancer tissues was not related to the surgical pathological staging, but was related to pathological staging; SKF96365 caused a dosedependent decline in cell amount of HEC-1 A cell. The expression quantity of TRPC6 in whole lysates of the celltransfected with target-TRPC6 small interference RNA(siRNA)was(38.51±6.21)% of that found in the cells transfected with non-silencing RNA;[3 H]thymidine incorporation in HEC-1 A transfected with target-TRPC6 siRNA was also reduced,siRNA inhibited HEC-l A cells proliferation,compared with the cells transfected with non-silencing RNA.CONCLUSION:s TRPC6 channels mignt be closely related to the proliferation of endometrial cancer cells and down regulation of its expression may suppress its development.