Endocytosis of Peptidase Inhibitor SerpinE2 promotes Myocardial Fibrosis through activating ERK1/2 and ß-catenin Signaling Pathways.

Cardiac fibrosis is one of the common pathological processes in many cardiovascular diseases characterized by excessive extracellular matrix deposition. SerpinE2 is a kind of protein that inhibits peptidase in extracellular matrix and up-regulated tremendously in mouse model of cardiac fibrosis induced by pressure-overloaded via transverse aortic constriction (TAC) surgery. However, its effect on cardiac fibroblasts (CFs), collagen secretion and the underlying mechanism remains unclear. In this study, DyLight® 488 green fluorescent dye or His-tagged proteins were used to label the exogenous serpinE2 protein. It was showed that extracellular serpinE2 translocated into CFs by low-density lipoprotein receptor-related protein 1 (LRP1) and urokinase plasminogen activator receptor (uPAR) of cell membrane through endocytosis. Knockdown of LRP1 or uPAR reduced the level of serpinE2 in CFs and down-regulated the collagen expression. Inhibition of the endocytosis of serpinE2 could inhibit ERK1/2 and ß-catenin signaling pathways and subsequently attenuated collagen secretion. Knockdown of serpinE2 attenuates cardiac fibrosis in TAC mouse. We conclude that serpinE2 could be translocated into cardiac fibroblasts due to endocytosis through directly interact with the membrane protein LRP1 and uPAR, and this process activated the ERK1/2, ß-catenin signaling pathways, consequently promoting collagen production.

The mRNA expression of visfatin and lipocalin-2 in peripheral blood mononuclear cells from patients with pulmonary tuberculosis.

BACKGROUND: In this study, we aimed to assess mRNA expressions of visfatin and lipocalin-2 in peripheral blood mononuclear cells (PBMCs) from patients with pulmonary tuberculosis (PTB). METHODS: Overall, 79 PTB patients and 71 healthy controls were enrolled. In PBMCs, mRNA expressions of visfatin and lipocalin-2 were detected using real-time quantitative polymerase chain reaction (qRT-PCR), and the diagnostic value of these adipokine mRNAs in PTB patients was calculated through receiver operating characteristic (ROC) analysis. RESULTS: In PBMCs from PTB patients, the visfatin mRNA level was significantly higher than in healthy controls (P < .001), with no significant association between the lipocalin-2 mRNA level and PTB patients (P = .933). In PTB patients, lipocalin-2 mRNA expression positively correlated with the erythrocyte sedimentation rate (ESR) (P = .010). However, the visfatin mRNA level was not associated with any major clinical and laboratory parameter in PTB patients. The ROC curve demonstrated that visfatin could help distinguish PTB patients from healthy controls, with an optimal cutoff value of 0.645 and a corresponding sensitivity of 79.7%. CONCLUSIONS: The altered visfatin mRNA expression indicated that this adipokine might play a role in PTB and could be an auxiliary biomarker for PTB diagnosis.

Antiangiogenic effect of crocin on breast cancer cell MDA-MB-231.

BACKGROUND: Crocin is the major chemical constituent of the Chinese herb saffron. A number of studies have indicated that crocin induces an antitumor effect by inhibiting proliferation and inducing the apoptosis of tumor cells. However, the effect of crocin on tumor angiogenesis remains unknown. METHODS: The effects of prolonged crocin exposure on breast cancer cell MDA-MB-231, human umbilical vein endothelial cells (HUVECs) and mice were examined. RESULTS: Crocin had a profound effect on the morphology and proliferation rate of MDA-MB-231 and HUVECs. Furthermore, crocin induced apoptosis and cell cycle arrest at the G2/M phase in MDA-MB-231 cells in a dose-dependent manner. This confirms that crocin induces the inhibition of HUVECs. Furthermore, the expression of CD34 in tumor tissues decreased after crocin treatment. CONCLUSIONS: Crocin has an anti-angiogenesis effect that may be correlated to the decreased expression of CD34. Crocin is likely to be involved in the regulation of molecules in the angiogenesis pathway.

Identification, Expression Analysis of the Hsf Family, and Characterization of Class A4 in Sedum Alfredii Hance under Cadmium Stress.

Sedum alfredii Hance, a cadmium (Cd)/zinc (Zn)/lead (Pb) co-hyperaccumulating species, is a promising phytoremediation candidate because it accumulates substantial amounts of heavy metal ions without showing any obvious signs of poisoning. The heat shock transcription factor (Hsf) family plays crucial roles in plant growth, development, and stress responses. Although the roles of some Hsfs in abiotic stress have been well studied in model plants, the Hsf family has not been systematically investigated in heavy metal hyperaccumulators. Here, we comprehensively analyzed the Hsf gene family in S. alfredii based on a transcriptome under Cd stress. There were 22 Hsf members that were identified and phylogenetically clustered into three classes, namely, SaHsfA, SaHsfB, and SaHsfC. All of the three classes shared similar motifs. The expression profiles of the 22 Hsf members showed significant differences: 18 SaHsfs were responsive to Cd stress, as were multiple SaHsp genes, including SaHsp18.1, SaHsp22, SaHsp26.5, SaHsp70, SaHsp90, and SaHsp101. Two class A4 members, SaHsfA4a and SaHsfA4c, exhibited transcriptional activation activities. Overexpression of SaHsfA4a and SaHsfA4c in transgenic yeast indicated an improved tolerance to Cd stress and Cd accumulation. Our results suggest SaHsfs play important regulatory roles in heavy metal stress responses, and provide a reference for further studies on the mechanism of heavy metal stress regulation by SaHsfs.

Expression and Clinical Significance of Sushi Domain- Containing Protein 3 (SUSD3) and Insulin-like Growth Factor-I Receptor (IGF-IR) in Breast Cancer.

BACKGROUND: To investigate the expression of insulin-like growth factor-I receptor (IGF-IR) and sushi domaincontaining protein 3 (SUSD3) in breast cancer tissue, and analyze their relationship with clinical parameters and the correlation betweenthe two proteins. MATERIALS AND METHODS: The expression of IGF-IR and SUSD3 in 100 cases of breast cancer tissues and adjacent normal breast tissues after surgery was detected by immunohistochemical technique MaxVisionTM, and the relationship with clinical pathological features was further analyzed. RESULTS: The positive rate of IGF-IR protein was 86.0% in breast cancer, higher than 3.0% in adjacent normalbreast tissue (P<0.05) .The positive expression rate of SUSD3 protein was 78.0% in breast cancer, higher than 2.0% in adjacent normal breast tissue (P<0.05). The expression of IGF-IR and SUSD3 was related to estrogen receptor and pathological types (P<0.05),but not with age, stage, the expression of HER-2 and Ki-67 (P>0. 05). The expression of IGF-IR and SUSD3 in breast cancer tissue was positively related (r= 0.553, P<0.01). CONCLUSIONS: The expression of IGF-IR and SUSD3 may be correlated to the occurrence and development of breast cancer. The combined detection of IGF-IR, SUSD3 and ER may play an important role in judging prognosis and guiding adjuvant therapy after surgery of breast cancer.