Research progress on the role of bile salts in ischemic-type biliary lesion after liver transplantation / 器官移植

Ischemic-type biliary lesion (ITBL) refers to biliary tract injury caused by insufficient blood supply of hepatic artery, which is one of the main factors affecting the long-term survival and quality of life of liver transplant recipients. The incidence of ITBL is associated with cold and warm ischemia, acute and chronic rejection, cytomegalovirus infection and the bile effect, etc. The occurrence of ITBL is a complicated process involving with multiple factors and steps. The therapeutic option of ITBL is extremely limited. A large proportion of ITBL patients should undergo repeated liver transplantation. ITBL has become one of the most critical factors preventing further advancement of liver transplantation. Hence, it is of significance to strengthen prevention and explore more effective modalities. Recent studies have found that toxic injury of bile salts plays a central role in ITBL. Active regulation of bile components, regulation of bile acid-related receptor expression and blockage or activation of bile acid-related signaling pathways probably have potentials in the prevention and treatment of ITBL. In this article, the cytotoxicity of bile salts and the mechanism of bicarbonate umbrella in the incidence and progression of ITBL after liver transplantation were reviewed, aiming to provide reference for the diagnosis and treatment of ITBL.

Bile acid signaling and biliary functions

This review focuses on various components of bile acid signaling in relation to cholangiocytes. Their roles as targets for potential therapies for cholangiopathies are also explored. While many factors are involved in these complex signaling pathways, this review emphasizes the roles of transmembrane G protein coupled receptor (TGR5), farnesoid X receptor (FXR), ursodeoxycholic acid (UDCA) and the bicarbonate umbrella. Following a general background on cholangiocytes and bile acids, we will expand the review and include sections that are most recently known (within 5-7 years) regarding the field of bile acid signaling and cholangiocyte function. These findings all demonstrate that bile acids influence biliary functions which can, in turn, regulate the cholangiocyte response during pathological events.

Effects of Increased Uric Acid Intake on the Abundance of Urate-anion exchanger and Organic Anion Transporter Proteins in the Rat Kidney

Renal handling of uric acid mainly occurs in the proximal tubule, and bidirectional transport of urate may involve apical absorption via the urate-anion exchanger (URAT1) and basolateral uptake via organic anion transporters (OAT1 and OAT3). In rat kidneys, we investigated whether the protein abundance of URAT1, OAT1, and OAT3 is affected by the increase in uric acid intake. Male Sprague-Dawley rats were randomly divided into control and uric acid-supplemented groups, and uric acid-supplemented rats were given 0.75 g of uric acid per 180 g body weight per day for 8 days. After the animal experiment, kidneys were harvested and semi-quantitative immunoblotting was carried out from cortical homogenates using polyclonal peptide-derived antibodies to URAT1, OAT1, and OAT3. Serum uric acid level showed an increasing tendency (p=0.055) in the uric acid-supplemented rats (2.60+/- 0.27 mg/dL) compared with control rats (1.97+/-0.29 mg/dL), whereas urinary uric acid excretion was not significantly different between the uric acid-supplemented rats (3.27+/-0.40 mg/d) and control rats (2.61+/-0.34 mg/d). URAT1 protein abundance in cortical homogenates was not significantly different between the uric acid-supplemented rats (132+/-14%) and control rats (100+/-7%). However, OAT1 protein abundance was significantly (p<0.05) increased in the uric acid-supplemented rats (148+/-13%) compared with the control rats (100+/-8%). OAT3 protein abundance was not significantly different between the uric acid-supplemented rats (131+/-12%) and control rats (100+/-17%). In conclusion, OAT1 may have a regulatory role in response to the increase in uric acid intake in the rat kidney. The up-regulation of OAT1 would exert stimulation of urinary uric acid excretion and might contribute to protection from hyperuricemia.

Family based analysis of quantitative changes of erythrocyte membrane proteins in essential hypertension.

Our previous studies have found significant quantitative changes in the erythrocyte membrane proteins in essential hypertension (EH). The purpose of the present study was to quantify genetic and environmental contributions to quantitative variability of erythrocyte membrane proteins in EH. We studied 115 hypertensive patients, 126 normotensive subjects, 235 of their first-degree relatives and 24 twin pairs by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. The decomposition of total phenotypic variance of erythrocyte membrane proteins to genetic and environmental components was performed by the least squares method. We found that genetic factors play a significant role in the control of quantitative changes in erythrocyte membrane proteins in EH. The genetic contribution to anion exchanger variation was stronger in hypertensives (88%) than in normotensives (36%), and was attributed exclusively to additive polygenic effects. Variation in glucose transporter was under marked control of major gene effect (74%). Importantly, variations in anion and glucose transporters in EH but not in healthy controls were strongly affected by common underlying genes with strong pleiotropic effects (r=0.921, P<0.05). These data provide evidence to support the genetic source of quantitative changes in membrane proteins in EH. Furthermore, the pleiotropic effects of common underlying genes seem to be responsible for variations in the transport proteins likely associated with genetic susceptibility to essential hypertension.