OBJECTIVES: To summarize the clinical and genetic characteristics of end-stage renal disease caused by PLCE1 gene mutations. METHODS: A retrospective analysis of the clinical and genetic features of three children from a family with PLCE1 gene mutations was conducted, along with a literature review of hereditary kidney disease cases caused by PLCE1 gene mutations. RESULTS: The proband was an 8-year-old male presenting with nephrotic syndrome stage 4 chronic kidney disease. Renal biopsy showed focal segmental glomerulosclerosis. Two years and five months after kidney transplantation, the patient had persistent negative proteinuria and normal renal function. Whole-exome sequencing identified two pathogenic heterozygous variants: c.961C>T and c.3255_3256delinsT, with c.3255_3256delinsT being a novel mutation. Family screening revealed no renal involvement in the parents, but among five siblings, one brother died at age of 4 years from end-stage renal disease. A 7-year-old sister presented with proteinuria and bilateral medullary sponge kidney, with proteinuria resolving after one year of follow-up. A 3-year-old brother died after kidney transplantation due to severe pneumonia. The literature review included 45 patients with hereditary kidney disease caused by PLCE1 gene mutations. The main clinical phenotype was nephrotic syndrome (87%, 39/45), and renal pathology predominantly showed focal segmental glomerulosclerosis (57%, 16/28). No mutation hotspots were identified. CONCLUSIONS Compound heterozygous mutations in the PLCE1 gene can lead to rapid progression of the disease to end-stage renal disease, with favorable outcomes following kidney transplantation. Family screening is crucial for early diagnosis, and medullary sponge kidney may be a novel phenotype associated with these gene mutations.
Humans ; Male ; Proteinuria/genetics* ; Kidney Failure, Chronic/etiology* ; Child ; Mutation ; Female ; Child, Preschool ; Retrospective Studies ; Phosphoinositide Phospholipase C

Humans ; Colorectal Neoplasms/genetics* ; Esophageal Neoplasms ; Genetic Predisposition to Disease ; Genotype ; Phosphoinositide Phospholipase C/genetics* ; Polymorphism, Single Nucleotide

Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; MicroRNAs/genetics* ; Phospholipase C delta ; Prostatic Neoplasms/genetics*

In women with preeclampsia (PE), endothelial cell (EC) dysfunction can lead to altered secretion of paracrine factors that induce peripheral vasoconstriction and proteinuria. This study examined the hypothesis that PE sera may directly or indirectly, through human umbilical vein ECs (HUVECs), stimulate phospholipase C-gamma1-1,4,5-trisphosphate (PLC-gamma1-IP3) signaling, thereby increasing protein kinase C-alpha (PKC-alpha) activity, collagen I expression and intracellular Ca2+ concentrations ([Ca2+]i) in human umbilical artery smooth muscle cells (HUASMCs). HUASMCs and HUVECs were cocultured with normal or PE sera before PLC-gamma1 silencing. Increased PLC-gamma1 and IP3 receptor (IP3R) phosphorylation was observed in cocultured HUASMCs stimulated with PE sera (P<0.05). In addition, PE serum significantly increased HUASMC viability and reduced their apoptosis (P<0.05); these effects were abrogated with PLC-gamma1 silencing. Compared with normal sera, PE sera increased [Ca2+]i in cocultured HUASMCs (P<0.05), which was inhibited by PLC-gamma1 and IP3R silencing. Finally, PE sera-induced PKC-alpha activity and collagen I expression was inhibited by PLC-gamma1 small interfering RNA (siRNA) (P<0.05). These results suggest that vasoactive substances in the PE serum may induce deposition in the extracellular matrix through the activation of PLC-gamma1, which may in turn result in thickening and hardening of the placental vascular wall, placental blood supply shortage, fetal hypoxia-ischemia and intrauterine growth retardation or intrauterine fetal death. PE sera increased [Ca2+]i and induced PKC-alpha activation and collagen I expression in cocultured HUASMCs via the PLC-gamma1 pathway.
Adult ; Apoptosis ; Calcium/*metabolism ; Cell Line ; Cell Survival ; Cells, Cultured ; Coculture Techniques ; Collagen Type I/analysis/*metabolism ; Female ; Human Umbilical Vein Endothelial Cells ; Humans ; Muscle, Smooth, Vascular/*cytology/metabolism ; Phospholipase C gamma/genetics/*metabolism ; Pre-Eclampsia/*blood/*metabolism/pathology ; Pregnancy ; Protein Kinase C-alpha/metabolism ; RNA Interference ; *Signal Transduction ; Young Adult

As prediction of rapidly aging society, bone health is considered increasingly important and received more attention than ever. Bone health is regulated by balancing between bone resorptive osteoclasts and bone formative osteoblasts. Disruption of balance between bone-resorbing osteoclasts and bone-forming osteoblasts results in bone disease. Natural products have recently received much attention as an alternative tool for the development of novel therapeutic strategy. Baicalein is reported it has anti-cancer, anti-inflammatory and antioxidant effects. Baicalein also has been known that it has both promotive effect on MC3T3-E1 cell line and inhibitory effect on RAW 264.7 cell line. However, the inhibitory mechanism of baicalein using bone marrow derived macrophages (BMMs) on osteoclast differentiation remains not clear. In this study, the suppressive mechanism by baicalein on osteoblast differentiation was evaluated. Bicalein inhibited receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation in BMMs in a dose dependent manner without any toxicity. Baicalein suppressed phosphorylation of protein kinaseB (Akt), c-Jun N-terminal kinases (JNK) and phosphoinositide-specific phospholipaseCgamma2 (PLCgamma2). Furthermore, Baicalein suppressed the induction of RANKL-induced c-Fos and Nuclear factor of activated T cell c1 (NFATc1), essential genes on osteoclastogenesis. In BMMs, Bicalein inhibited the mRNA expression of tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), cathepsinK, dendritic cell-specific transmembrane protein (DC-STAMP). Moreover, baicalein promoted differentiation of osteoblast on bone marrow stromal cells (BMSCs). Taken together, these results suggest that baicalein has a potential for treating bone lytic diseases, such as osteoporosis, periodontitis, and rheumatoid arthritis.
Acid Phosphatase ; Aging ; Antioxidants ; Arthritis, Rheumatoid ; Biological Products ; Bone Diseases ; Bone Marrow* ; Cell Line ; Genes, Essential ; Macrophages* ; Mesenchymal Stromal Cells ; Osteoblasts ; Osteoclasts* ; Osteoporosis ; Periodontitis ; Phospholipase C gamma ; Phosphorylation ; Phosphotransferases ; RANK Ligand ; RNA, Messenger

OBJECTIVETo investigate the changes in the expression of phospholipase C-gamma1tyr783 (PLC-&gamma;1tyr783) in the condylar cartilage of a young rat during functional mandibular protraction. This work also explores the function of PLC-&gamma;1tyr783 in the rat mandibular condylar cartilage bone remodeling, which could provide experimental evidence for clinical bone ortho- pedic work.

METHODSA total of 60 four-week-old male Sprague-Dawley (SD) rats were used in this study. The rats were divided equally and randomly into experimental group and control group. The functional appliances that were fitted to the upper incisors of the animals in the experimental group were worn 24 h a day after the rats were fed for 7 d with homemade pellet feed. The animals in the experimental group, along with their matched controls, were sacrificed after 1, 3, 7, 14, 21, and 28 d. The bilateral condylar was fixed, decalcified, dehyded, and then conventional paraffin embedded. Immunohisto- chemistry of PLC-&gamma;1tyr783 was applied to observe its express distribution and variation.

RESULTSThe expression of PLC-&gamma;1tyr783 decreased gradually in the control group, which showed age-related changes (P > 0.05). On the 14th day, PLC-&gamma;1tyr783 expres- sion in the experimental group was significantly higher than that in the control group. PLC-&gamma;1tyr783 expression began to appear statistically and significantly different between the two groups (P < 0.01).

CONCLUSIONPLC-&gamma;1tyr783 is involved in the bone remodeling process of the rat condylar cartilage after functional mandibular-protraction.

Animals ; Bone Remodeling ; Cartilage ; Male ; Mandibular Condyle ; Phospholipase C gamma ; Phosphoric Diester Hydrolases ; Rats ; Rats, Sprague-Dawley

OBJECTIVEThe purpose of the present study was to observe the changes in CD4+CD25+Nrp1+Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved.

METHODSICR mice and mouse lymphoma cell line (EL-4 cells) was used. The expressions of CD4, CD25, Nrp1, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-&beta;1, IL-10, PKA and cAMP were estimated with ELISA.

RESULTSAt 12 h after irradiation, the expression of Nrp1 increased significantly in 4.0 Gy group, compared with sham-irradiation group (P<0.05) in the spleen and thymus, respectively, when ICR mice received whole-body irradiation (WBI). Meanwhile the synthesis of Interleukin 10 (IL-10) and transforming growth factor-&beta;1 (TGF-&beta;1) increased significantly after high dose irradiation (HDR) (> or = 1.0 Gy). In addition, the expression of cAMP and PKA protein increased, while PKC-α, calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-&beta;1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation, this did not limit the up-regulation of CD4+CD25+Nrp1+Treg cells after ionizing radiation.

CONCLUSIONThese results indicated that HDR might induce CD4+CD25+Nrp1+Treg cells production and stimulate TGF-&beta;1 secretion by regulating signal molecules in mice.

Animals ; Calcineurin ; genetics ; metabolism ; Cyclic AMP ; metabolism ; Dose-Response Relationship, Radiation ; Female ; Gene Expression Regulation ; radiation effects ; Immunosuppression ; Interleukin-10 ; genetics ; metabolism ; Lymphocyte Subsets ; physiology ; Male ; Mice ; Neuropilin-1 ; genetics ; metabolism ; Phosphoinositide Phospholipase C ; genetics ; metabolism ; Protein Kinases ; genetics ; metabolism ; Signal Transduction ; Transforming Growth Factor beta ; genetics ; metabolism ; Whole-Body Irradiation ; adverse effects

OBJECTIVETo study the expression of phospholipase C epsilon-1(PLCE1) and its clinical significance in gastric cancer.

METHODSSurgical specimens were collected from 125 patients who underwent radical gastrectomy between 2005 and 2007 in the Zhejiang Provincial Peoples' Hospital. Expression level of PLCE1 protein was measured by immunohistochemistry in these 125 surgical specimens, which included primary gastric cancer and matched adjacent normal gastric mucosa tissues, and then 41 pairs of above specimens were selected randomly to examine the expression level of PLCE1 mRNA by quantitative reverse transcription PCR(qRT-PCR).

RESULTSImmunohistochemistry and qRT-PCR showed that both protein and mRNA level of PLCE1 were up-regulated in gastric cancer compared with paired normal gastric mucosa. Univariate analysis demonstrated that the expression of PLCE1 was significantly associated with differentiation degree, invasion depth, lymph node metastasis, distant metastasis, and TNM stage (all P<0.01). The 5-year survival rate of positive PLCE1 group was significantly lower as compared to negative group (31.2% vs. 54.0%, P<0.01). However, the expression of PLCE1 was not an independent prognostic factor for gastric cancer (P>0.05).

CONCLUSIONSPLCE1 is up-regulated in gastric cancer, which is associated with the malignant biological behaviors of gastric cancer. High expression of PLCE1 suggests poor prognosis.

Biomarkers, Tumor ; analysis ; Gastrectomy ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Staging ; Phosphoinositide Phospholipase C ; metabolism ; Prognosis ; RNA, Messenger ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms ; enzymology ; pathology ; Survival Rate ; Up-Regulation

BACKGROUNDThe pathogenesis of gastric cancer (GC) involves environmental and genetic factors. Recently, two genome-wide association studies found that phospholipase C epsilon 1 (PLCE1) polymorphisms might be related to GC risk, and several studies further validated this finding. However, these studies yielded inconsistent results.

METHODSA comprehensive database search was performed to identify eligible studies. Odds ratios with 95% confidence intervals were calculated to assess the strength of the association between PLCE1 rs2274223, rs753724, and rs11187842 and risk of GC. Subgroup analyses, publication bias, and sensitivity analyses were also conducted.

RESULTSEleven studies (12 cohorts) were included in the meta-analysis. Based on 13 676 cases and 23 569 controls, a significant association between PLCE1 rs2274223 and GC risk was detected under various genotypic models. In the subgroup analyses, the association was significant for cardia GC, but weak for non-cardia GC. The association under the heterozygote model was detected for PLCE1 rs753724 and rs11187842 based on three studies involving 2768 cases and 3890 controls.

CONCLUSIONSOur findings demonstrate that the presence of the G allele at rs2274223 of the PLCE1 gene may contribute to susceptibility to GC, especially cardia GC. PLCE1 rs753724 and rs11187842 are associated with GC risk under the heterozygote model. Further well-designed large studies are warranted to validate these findings.

Genetic Predisposition to Disease ; genetics ; Genome-Wide Association Study ; Humans ; Phosphoinositide Phospholipase C ; genetics ; Polymorphism, Genetic ; genetics ; Stomach Neoplasms ; genetics

Phospholipase C epsilon-1 (PLCE1) is a phospholipase C isoenzyme encoded by PLCE1 gene, and has more complicated molecular structure and function than other subtypes. Phospholipase C epsilon-1 is accepted the dual regulation by the upstream G proteins and GTP enzymes of Ras family. The downstream signal of PLCE1 is not only cause the Ca2+ flow and protein kinase C(PKC) activation, but also can be used as the GTP enzyme guanylic acid conversion factor of Ras superfamily, so as to regulate the expression of certain genes, adjusting cell growth and differentiation processes. PLCE1 plays a very important role in the signal transduction in the regulation of cell growth, differentiation, proliferation and apoptosis. Previous studies showed that phospholipase C epsilon-1 played an important role in the development of malignant tumors (especially the digestive tumors), heart disease, nephrotic syndrome and other diseases, but there are some questions about the mechanisms of PLCE1 involved in allergic rhinitis, this article will make an overview about PLCE1 promotes allergic rhinitis CD4+ T cells differentiate to Th2 cells by PKC-NF-κB pathway and Ras-MAPK pathway.
Apoptosis ; Calcium ; metabolism ; Cell Cycle ; Cell Differentiation ; physiology ; Cell Proliferation ; physiology ; Enzyme Activation ; Gene Expression ; Humans ; NF-kappa B ; Phosphoinositide Phospholipase C ; genetics ; physiology ; Protein Kinase C ; metabolism ; Rhinitis, Allergic ; enzymology ; Signal Transduction ; Th2 Cells ; cytology