Hepatic DDAH1 mitigates hepatic steatosis and insulin resistance in obese mice: Involvement of reduced S100A11 expression

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1f/f), Ddah1HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1f/f mice. On the contrary, overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice. RNA-seq analysis showed that DDAH1 affects NF-κB signaling, lipid metabolic processes, and immune system processes in fatty livers. Furthermore, DDAH1 reduces S100 calcium-binding protein A11 (S100A11) possibly via NF-κB, JNK and oxidative stress-dependent manner in fatty livers. Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1HKO mice. In summary, our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice. Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.

Expression and clinical significance of S100A11 in non-small cell lung cancer / 国际肿瘤学杂志

Objective To investigate the expression of S100A11 protein in non-small cell lung cancer (NSCLC) and its association with clinical and pathological characteristics.Methods The expressions of S100A11 protein in 112 NSCLC tumor tissues (group A), tumor-adjacent tissues (group B) and 10 normal lung tissues (group C) were detected by immunohistochemical SP method.The association of S100A11 expression with clinical pathological characteristics was analyzed.Results The percentage of the cases with high expression cases of S100A11 protein was 78.6％ (88/112) , and the low expression rate was 21.4 ％ (24/112) in group A.The low expression rate of S100A11 protein was 100.0％ (112/112) in group B.The negative expression rate of S100A11 protein was 100.0％ (10/10) in group C.The difference of S100A11 expression among the three groups was statistically significant (x2 =153.634, P ＜0.001).The S100A11 expression was associated with pathological type (x2 =6.807, P =0.009), differentiated degree (x2 =5.029, P =0.025), regional lymph node metastasis (x2 =11.721, P =0.001) in NSCLC, but it was not associated with gender (x2 =0.020, P =0.888) , age (x2 =0.816, P =0.366) and tumor size (x2 =0.406, P =0.524).Conclusion S100A11 is highly expressed in NSCLC, which is closely related with biological behavioral characteristics.S100A11 may participate in the occurrence and development of NSCLC, and it is expected to become the potential target of diagnosis and prognosis in patients with NSCLC.

Spinal Cord Injury Markedly Altered Protein Expression Patterns in the Affected Rat Urinary Bladder during Healing Stages

The influence of spinal cord injury (SCI) on protein expression in the rat urinary bladder was assessed by proteomic analysis at different time intervals post-injury. After contusion SCI between T9 and T10, bladder tissues were processed by 2-DE and MALDI-TOF/MS at 6 hr to 28 days after SCI to identify proteins involved in the healing process of SCI-induced neurogenic bladder. Approximately 1,000 spots from the bladder of SCI and sham groups were visualized and identified. At one day after SCI, the expression levels of three protein were increased, and seven spots were down-regulated, including heat shock protein 27 (Hsp27) and heat shock protein 20 (Hsp20). Fifteen spots such as S100-A11 were differentially expressed seven days post-injury, and seven proteins including transgelin had altered expression patterns 28 days after injury. Of the proteins with altered expression levels, transgelin, S100-A11, Hsp27 and Hsp20 were continuously and variably expressed throughout the entire post-SCI recovery of the bladder. The identified proteins at each time point belong to eight functional categories. The altered expression patterns identified by 2-DE of transgelin and S100-A11 were verified by Western blot. Transgelin and protein S100-A11 may be candidates for protein biomarkers in the bladder healing process after SCI.