| Background Acute Kidney Injury(AKI) and Chronic Kidney Disease(CKD) are both the most important public health problems facing humanity in the 21 st century. AKI is a common disease in clinic characterized by acute alterations in serum creatinine or urine output, often caused by a variety of agents with different clinical manifestations.CKD is an illness state of renal function slowly decreased because of many causes and eventually will develop into End stage takes diseases(ESRD), CKD is a set of clinical syndrome often affected by a variety of factors. Different diseases and risk factors can lead to this state. The number of confirmed cases with AKI and CKD around the world are increasing fast, it is serious danger to human health, the expense of medical care on CKD is so high that patients endured great economic burden. Prevention and treatment of CKD is quite grim. Epidemiologic study showed that half critically ill patients of adult will developed into AKI. In China, the prevalence of CKD is about 10.8% among aged 20 and over, shows an upward trend year by year. The total number of individuals with CKD are nearly 100 million. The morbidity and complication rates are very high, the number of CKD patients is still increasing fast but awareness rate of CKD related knowledge is very low. CKD bring not only physical and mental suffering to the patients, but also heavy financial burden to family and social. Early recognition and appropriate treatment and exploring of mechanism of such cases are extremely important to delay the decline of renal function, reduce the mortality rate and the economic burden. Kidney is an important endocrine and excretion organ, function and structure abnormalities of glomerular and tubular will cause the damage to the kidney function. Kidney disease developed to a certain stage will cause damage of glomerular and tubular. Normal renal tubular epithelial cells have strong secretion and proliferation activity, a variety factors of disease can result in abnormal structure and function in tubular epithelial cells, then tubular secretion and reabsorption function be affected, resulting in a series of metabolic disorder. Renal tubulointerstitial injury plays a vital role in the process and progress of AKI and CKD. In many primary and secondary glomerular diseases or some non-glomerular diseases, tubule and interstitial lesions can reflect the damage of kidney function and have a relation with the prognosis of these diseases. Multiple causes can induce tubular damage, like ischemia, hypoxia, inflammation, abnormal activation of renal tubule epithelial cells and so on. So research on function of renal tubular interstitial and renal tubular epithelial cells will help to clear the occurrence and progress mechanism of CKD, providing new targets for the prevention and therapeutic of CKD. S100A6, also known as Calcyclin, is a small molecule calcium binding protein belongs to the S100 family. The distribution of S100A6 had tissue and cell specificity, highly expressed in epithelial cells and fibroblast, closely related to the function of secretion and proliferation. Through pre-experiment, we found that S100A6 expression significantly related to renal interstitial fibrosis in UUO mice. It has been reported that in the process of recovery after acute kidney injury, S100A6 play an important role in wound repair in renal tubular epithelial cells. S100A6 expression is significantly increased in renal clear cell carcinoma(cc RCC) tumor tissue. Calcylin binding protein/Siah-1 interacting protein(CacyBP/SIP), Played an important role in the process of cell proliferation, differentiation and tumorigenesis, cell cytoskeleton, gene transcription and ubiquitin. CacyBP/SIP can interact with Siah-1 and Skp1, promoting ?-catenin degradation via ubiquitination. According to the literature, the expression of CacyBP/SIP in renal cell carcinoma tissues significantly lower than the adjacent tissues, overexpression of CacyBP/SIP can inhibit the proliferation of cancer cells and tumor. As mentioned above, S100A6 plays an important part in the recovery process of acute kidney injury, S100A6 and CacyBP/SIP are all involved in the development of kidney tumors. However, their role in CKD is unclear. In this study, we used Immunological Histological Chemistry(IHC) to detect the expression of S100A6 and CacyBP/SIP in renal tissue of AKI and CKD patients and Enzyme-Linked Immunosorbent Assay(ELISA) in serum. The relationship between S100A6 or CacyBP/SIP and CKD are preliminarily analyzed.Aims Through detection the expression of S100A6 and its binding protein CacyBP/SIP in renal tissue and peripheral blood of control group and patients with acute or chronic kidney disease, to discuss their changes in expression and clinical significance. Aims to provide new ideas for the further studies on diagnosis and treatment and clear the progress mechanism of acute and chronic kidney disease.Methods 1. We use IHC to detect the expression of S100A6 in kidney tissue of mice model, the mice model was induced by unilateral ureteral obstruction(UUO). 2. The expression of S100A6 and CacyBP/SIP in kidney tissues of normal and different pathological type of acute or chronic kidney disease were tested by IHC. 3. The concentration of S100A6 and CacyBP/SIP in serum of normal and CKD were measured with ELISA.Results 1. IHC in sham and UUO mice kidney: S100A6 mainly expressed in the glomeruli and renal interstitium, nucleus weakly positive in sham mice kidney. The expression of S100A6 increases gradually with the degree of renal tubulointerstitial injury, positively related to the degree of renal tubulointerstitial injury. 2. S100A6 and CacyBP/SIP in normal and patients with acute or of chronic kidney disease: S100A6 was localized mainly in the mesangial area, capillary wall and Baumann's capsule wall of renal glomerular and distal renal tubules epithelial cells and a small amount of renal interstitial cells, in nucleus and cytoplasm and nuclear membrane, but not expressed in the proximal renal tubules epithelial cells. The expression of S100A6 significantly increased in patients with AKI especially in proximal renal tubular epithelial cell cytoplasm and nucleus of distal renal tubular epithelial cells, positive and/or strong positive. S100A6 changed the subcellular localization in acute injury of renal tubules, migrated to the nucleus. The expression of S100A6 in kidney tissues of CKD patients showed a dynamic variation process, according to the degree of renal tubular interstitial damage, gradually rising from mild to moderate renal tubular interstitial injury group and decreased in severe group but still higher than control group. CacyBP/SIP is mainly expressed in cytoplasm and cell membrane of renal tubular epithelial cells in normal renal tissues, there is no significant difference between the proximal and the distal, but not expressed in glomerular cells. The expression of CacyBP/SIP significantly decreased in AKI and CKD.As the degree of renal tubular interstitial damage is aggravating, the expression of CacyBP/SIP decreased progressively in CKD, especially in the cytoplasm. 3. ELISA results: The concentration of S100A6 and CacyBP/SIP in serum of patients with CKD were significantly higher than the normal group, S100A6( Control, n=58,1256.91±536.54 CKD n=119,1772.44 ±653.18(P<0.001)), CacyBP/SIP(Control, n=58,2034.79±684.91 CKD n=118,2883.99 ±780.88(P<0.05)). The concentration of S100A6 and CacyBP/SIP enhanced obviously as the CKD stage increased and related to creatinine, e GFR but not related to the content of cystatin C, hemoglobin, uric acid, total cholesterol, mean arterial pressure etc. The results suggest that the concentration of S100A6 and CacyBP/SIP were limited to recognize patients with early CKD, may has a good prediction effect of the progress of CKD.Conclusion 1. The expression of S100A6 was positively related to the degree of renal tubulointerstitial injury. 2. S100A6 mainly expression in glomeruli and distal renal tubular epithelial cells in normal kidney tissues, but not expressed in the proximal convoluted tubules. In AKI and CKD renal tissue, positive expression appeared in proximal renal tubular epithelial cells and expression in nucleus increased in distal renal tubular epithelial cells. The subcellular localization of S100A6 in AKI changed from the cytoplasm into the nucleus, showed a dynamic variation process in CKD kidney tissues, according to the degree of renal tubular interstitial damage, The expression of S100A6 increases first and then gradually decreased. CacyBP/SIP expression in all renal tubular epithelial cells in normal kidney tissues, but not expressed in glomerular cells.The expression of CacyBP/SIP significantly decreased in AKI and CKD.As the degree of renal tubular interstitial damage is aggravating, the expression of CacyBP/SIP gradually decreased in CKD renal tissue. 3. The concentration of S100A6 and CacyBP/SIP in peripheral blood of CKD patients were significantly higher than the control group. S100A6 and CacyBP/SIP expression in the serum is related to the stage of CKD, may have a good prediction effect to the progression of CKD. |
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