Association of Serum PSP/REG Iα with Renal Function in Type 2 Diabetes Mellitus

Purpose. Pancreatic stone protein/regenerating protein I (PSP/REG Iα) is a secretory protein mainly detected in the pancreas. Recent studies revealed increased serum PSP/REG Iα levels may reflect renal dysfunction. The purpose of this study was to detect the relationship between PSP/REG Iα and renal function in subjects with and without type 2 diabetes mellitus (T2DM). Methods. This cross-sectional study was conducted at Zhongda Hospital, affiliated with Southeast University in China. Serum PSP/REG Iα levels were measured using a method of enzyme-linked immunosorbent assay. Baseline characteristics and biochemical parameters, such as blood urea nitrogen (BUN), serum creatinine (SCr), and uric acid (UA), were collected. The estimated glomerular filtration rate (eGFR) of each individual was calculated using the diagnostic criteria for renal function. Correlations between PSP/REG Iα and renal function parameters were analyzed by Spearman’s rank correlation coefficient using SPSS 20.0 software. Results. Serum PSP/REG Iα levels were significantly higher in T2DM patients than those without T2DM (P<0.05). The level of PSP/REG Iα was positively correlated with age, SCr, and BUN and negatively correlated with eGFR. The ordinal multiple logistic regression analysis further illustrated that PSP/REG Iα levels were negatively related with eGFR in both groups after adjusting for other parameters. Conclusions. Serum PSP/REG Iα level is significantly upregulated in T2DM patients and reflects renal function in both T2DM and nondiabetic control groups. The relationship between PSP/REG Iα and eGFR suggested that PSP/REG Iα might be a potential indicator of renal dysfunction.

Association of Serum PSP/REG Iαwith Renal Function in Pregnant Women

Pancreatic stone protein/regenerating protein Iα(PSP/REG Iα) is a secretory protein produced in the pancreas, but its expression has also been observed in the kidney. It may be associated with kidney dysfunction. This study investigates the possible association between PSP/REG Iαand kidney function in pregnant women. Serum PSP/REG Iαlevels were measured by a specific ELISA enzyme-linked immunosorbent assay. Maternal information and clinical and biochemical parameters were collected. Estimated glomerular filtration rate (eGFR) was calculated for all individuals to evaluate their renal function. Spearman’s correlation and multiple linear regression analyses were performed to assess the associations between PSP/REG Iαand eGFR, serum creatinine (Cr), blood urea nitrogen (BUN), and uric acid (UA). A total of 595 pregnant women were enrolled in the study. Participants with mildly reduced eGFR had higher PSP/REG Iαlevels [50.49 (35.02, 58.64)] than in the general population [26.84 (21.02, 33.07)] (p < 0.001). Included participants were stratified into PSP/REG Iαquartiles; significant differences were observed in the levels of eGFR, serum Cr, BUN, and UA. PSP/REG Iαwas negatively correlated with eGFR (r = −0.402, p < 0.001) and positively associated with serum Cr (r = 0.468, p < 0.001), BUN (r = 0.166, p < 0.001), and UA (r = 0.207, p < 0.001). The linear regression analysis indicated that PSP/REG Iαwas associated with UA, BUN, and eGFR. High PSP/REG Iαconcentrations were closely associated with renal dysfunction in pregnant women. Our study provides clinical evidence that serum PSP/REG Iαlevels could be a novel biomarker for assessment of renal function in pregnant women.

An Upper Bound for the Regularity of Symbolic Powers of Edge Ideals of Chordal Graphs

Assume that $G$ is a chordal graph with edge ideal $I(G)$ and ordered matching number $\nu_{o}(G)$. For every integer $s\geq 1$, we denote the $s$-th symbolic power of $I(G)$ by $I(G)^{(s)}$. It is shown that ${\rm reg}(I(G)^{(s)})\leq 2s+\nu_{o}(G)-1$. As a consequence, we determine the regularity of symbolic powers of edge ideals of chordal Cameron-Walker graphs.

Expression of Reg family genes in the gastrointestinal tract of mice treated with indomethacin

Regenerating gene ( Reg) family proteins, which are classified into four types, commonly act as trophic and/or antiapoptotic factors in gastrointestinal (GI) diseases. However, it remains unclear how these proteins coordinate their similar roles under such pathophysiological conditions. Here, we investigated the interrelationships of Reg family gene expression with mucosal cell proliferation and apoptosis in nonsteroidal anti-inflammatory drug (NSAID)-induced GI injury. GI injury was induced by subcutaneous injection of indomethacin into Reg I knockout (KO) and wild-type (WT) mice, and its severity was scored histopathologically. Temporal changes in the expression of Reg family genes, mucosal proliferation, and apoptosis were evaluated throughout the GI tract by real-time RT-PCR, Ki-67 immunoreactivity, and TUNEL assay, respectively. Reg I, Reg III family, and Reg IV were predominantly expressed in the upper, middle, and lower GI mucosa, respectively. Expression of Reg I and Reg III family genes was upregulated in specific portions of the GI tract after indomethacin treatment. Ki-67-positive epithelial cells were significantly decreased in the gastric and small-intestinal mucosa of Reg I KO mice under normal conditions. After treatment with indomethacin, the number of TUNEL-positive cells was significantly greater throughout the GI mucosa in Reg I KO mice than in WT mice. Expression of Reg I was independent of that of other Reg family genes in, not only normal GI tissues, but also indomethacin-induced GI lesions. Members of the Reg gene family show distinct profiles of expression in the GI tract, and Reg I independently plays a role in protecting the GI mucosa against NSAID-induced injury.

Synergistic Activations ofREG IαandREG IβPromoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human PancreaticβCells

Reg(Regenerating gene) gene was originally isolated from rat regenerating islets and its encoding protein was revealed as an autocrine/paracrine growth factor forβcells. RatReggene is activated in inflammatory conditions forβcell regeneration. In human, although five functionalREGfamily genes (REG Iα, REG Iβ, REG III, HIP/PAP, andREG IV) were isolated, their expressions inβcells under inflammatory conditions remained unclear. In this study, we found that combined addition of IL-6 and dexamethasone (Dx) inducedREG IαandREG Iβexpression in human 1.1B4βcells. Promoter assay revealed that a signal transducer and activator of transcription- (STAT-) binding site in each promoter ofREG Iα(TGCCGGGAA) andREG Iβ(TGCCAGGAA) was essential for the IL-6+Dx-induced promoter activation. A Janus kinase 2 (JAK2) inhibitor significantly inhibited the IL-6+Dx-inducedREG IαandREG Iβtranscription. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed that IL-6+Dx stimulation increased STAT3 binding to theREG Iαpromoter. Furthermore, small interfering RNA-mediated targeting of STAT3 blocked the IL-6+Dx-induced expression ofREG IαandREG Iβ. These results indicate that the expression ofREG IαandREG Iβshould be upregulated in humanβcells under inflammatory conditions through the JAK/STAT pathway.