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Cell Cycle (Georgetown, Tex.) Oct 2022Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in liver cancer, with a high rate of metastasis and recurrence. Circular RNA_0061395...
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in liver cancer, with a high rate of metastasis and recurrence. Circular RNA_0061395 (circ_0061395) has been shown to be involved in the advance of HCC. However, the interaction between circ_0061395 and microRNA (miRNA) in HCC has not been studied. Quantitative real-time polymerase-chain reaction (qRT-PCR) was used to detect the expression of related genes in liver cancer tissues and cells. The stability of circ_0061395 was verified by RNase R digestion. Through detection of cell malignant behavior and apoptosis, the capping experiment was carried out to verify the regulatory relationship between miR-1182 and circ_0061395 or SPARC/osteonectin, CWCV and Kazal-like domains proteoglycan 1 (SPOCK1). The expression of related proteins was detected by western blot. The interaction of miR-1182 with circ_0061395 or SPOCK1 has been notarized by Dual-luciferase reporter analysis and RNA immunoprecipitation (RIP) assay. Xenotransplantation experiments using BALB/C nude mice were used to confirm the function of circ_0061395 . Circ_0061395 and SPOCK1 were significantly expressed in liver cancer tissues and cells. Silencing circ_0061395 reduced the proliferation, migration, invasion, tube formation and tumor spheroid formation rate of Huh-7 and SNU-387 cells. MiR-1182 was a target of circ_0061395. Silencing circ_0061395 inhibited the malignant behavior of HCC cells by releasing miR-1182. In addition, SPOCK1 was the target of miR-1182. Overexpression of SPOCK1 partially restored the inhibitory effect of miR-1182 on cell proliferation. Animal experiments confirmed the anti-tumor effect of silence circ_0061395. Circ_0061395 induced the changes of the expression of SPOCK1 by regulating miR-1182, thereby mediating the process of HCC, and at least partially promoting the development of HCC cells, providing a novel targeted therapy for HCC.
Topics: Animals; Carcinogenesis; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Osteonectin; Proteoglycans; RNA, Circular
PubMed: 35775884
DOI: 10.1080/15384101.2022.2092177 -
Journal of Molecular and Cellular... Mar 2010The cardiac interstitium is a unique and adaptable extracellular matrix (ECM) that provides a milieu in which myocytes, fibroblasts, and endothelial cells communicate... (Review)
Review
The cardiac interstitium is a unique and adaptable extracellular matrix (ECM) that provides a milieu in which myocytes, fibroblasts, and endothelial cells communicate and function. The composition of the ECM in the heart includes structural proteins such as fibrillar collagens and matricellular proteins that modulate cell:ECM interaction. Secreted Protein Acidic and Rich in Cysteine (SPARC), a collagen-binding matricellular protein, serves a key role in collagen assembly into the ECM. Recent results demonstrated increased cardiac rupture, dysfunction and mortality in SPARC-null mice in response to myocardial infarction that was associated with a decreased capacity to generate organized, mature collagen fibers. In response to pressure overload induced-hypertrophy, the decrease in insoluble collagen incorporation in the left ventricle of SPARC-null hearts was coincident with diminished ventricular stiffness in comparison to WT mice with pressure overload. This review will focus on the role of SPARC in the regulation of interstitial collagen during cardiac remodeling following myocardial infarction and pressure overload with a discussion of potential cellular mechanisms that control SPARC-dependent collagen assembly in the heart.
Topics: Animals; Extracellular Matrix; Fibrillar Collagens; Humans; Mice; Models, Biological; Myocardium; Osteonectin
PubMed: 19577572
DOI: 10.1016/j.yjmcc.2009.06.018 -
Pathology Oncology Research : POR 2022Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) was a kind of extracellular matrix glycoprotein. SPARCL1 was strongly inhibited in most cancers. However,...
Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) was a kind of extracellular matrix glycoprotein. SPARCL1 was strongly inhibited in most cancers. However, the potential functions of SPARCL1 in the pan-cancer cohort have not been widely studied. We evaluated the transcriptional level and the prognostic value of SPARCL1 in 33 types of cancer and revealed the relationship between genetic alterations of SPARCL1 and the tumor mutation burden. Meanwhile, we assessed the correlations between SPARCL1 and tumor-infiltrating lymphocytes across cancers. The transcriptional level of SPARCL1 was inhibited in most cancers. Although SPARCL1 was down-regulated in most cancers, SPARCL1 might play a protective or detrimental role in different cancers. We demonstrated that mutation count was elevated in the altered SPARCL1 group in several cancers. Additionally, we found a significant positive correlation between SPARCL1 and macrophage infiltration levels in most cancers. Especially, marker sets of M2 macrophages were strongly related to SPARCL1 in cholangiocarcinoma, colon adenocarcinoma, rectum adenocarcinoma, and pancreatic adenocarcinoma. Our study found that SPARCL1 might work as a biomarker for prognosis and immune infiltration in pan-cancer analysis.
Topics: Humans; Prognosis; Cysteine; Adenocarcinoma; Osteonectin; Pancreatic Neoplasms; Colonic Neoplasms; Calcium-Binding Proteins; Extracellular Matrix Proteins
PubMed: 36483097
DOI: 10.3389/pore.2022.1610687 -
Molecular Psychiatry Jun 2023Central nervous system axons have minimal capacity to regenerate in adult brains, hindering memory recovery in Alzheimer's disease (AD). Although recent studies have...
Central nervous system axons have minimal capacity to regenerate in adult brains, hindering memory recovery in Alzheimer's disease (AD). Although recent studies have shown that damaged axons sprouted in adult and AD mouse brains, long-distance axonal re-innervation to their targets has not been achieved. We selectively visualized axon-growing neurons in the neural circuit for memory formation, from the hippocampus to the prefrontal cortex, and showed that damaged axons successfully extended to their native projecting area in mouse models of AD (5XFAD) by administration of an axonal regenerative agent, diosgenin. In vivo transcriptome analysis detected the expression profile of axon-growing neurons directly isolated from the hippocampus of 5XFAD mice. Secreted protein acidic and rich in cysteine (SPARC) was the most expressed gene in axon-growing neurons. Neuron-specific overexpression of SPARC via adeno-associated virus serotype 9 delivery in the hippocampus recovered memory deficits and axonal projection to the prefrontal cortex in 5XFAD mice. DREADDs (Designer receptors exclusively activated by designer drugs) analyses revealed that SPARC overexpression-induced axonal growth in the 5XFAD mouse brain directly contributes to memory recovery. Elevated levels of SPARC on axonal membranes interact with extracellular rail-like collagen type I to promote axonal remodeling along their original tracings in primary cultured hippocampal neurons. These findings suggest that SPARC-driven axonal growth in the brain may be a promising therapeutic strategy for AD and other neurodegenerative diseases.
Topics: Mice; Animals; Alzheimer Disease; Diosgenin; Osteonectin; Axons; Hippocampus; Disease Models, Animal; Mice, Transgenic
PubMed: 37085711
DOI: 10.1038/s41380-023-02052-9 -
British Journal of Pharmacology Jan 2017The SPARC (secreted protein acidic and rich in cysteine) protein is matricellular molecule regulating interactions between cells and their surrounding extracellular... (Review)
Review
The SPARC (secreted protein acidic and rich in cysteine) protein is matricellular molecule regulating interactions between cells and their surrounding extracellular matrix (ECM). This protein thus governs fundamental cellular functions such as cell adhesion, proliferation and differentiation. SPARC also regulates the expression and activity of numerous growth factors and matrix metalloproteinases essential for ECM degradation and turnover. Studies in SPARC-null mice have revealed a critical role for SPARC in tissue development, injury and repair and in the regulation of the immune response. In the lung, SPARC drives pathological responses in non-small cell lung cancer and idiopathic pulmonary fibrosis by promoting microvascular remodelling and excessive deposition of ECM proteins. Remarkably, although chronic airway conditions such as asthma and chronic obstructive pulmonary disease (COPD) involve significant remodelling in both the airway and vascular compartments, the role of SPARC in these conditions has thus far been overlooked. In this review, we discuss the role of SPARC in lung cancer and pulmonary fibrosis, as well as potential mechanisms by which it may contribute to the disease process in asthma and COPD.
Topics: Animals; Humans; Lung Neoplasms; Osteonectin; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis
PubMed: 27759879
DOI: 10.1111/bph.13653 -
PloS One 2021Collagen deposition contributes to both high mammographic density and breast cancer progression. Low stromal PTEN expression has been observed in as many as half of...
Collagen deposition contributes to both high mammographic density and breast cancer progression. Low stromal PTEN expression has been observed in as many as half of breast tumors and is associated with increases in collagen deposition, however the mechanism connecting PTEN loss to increased collagen deposition remains unclear. Here, we demonstrate that Pten knockout in fibroblasts using an Fsp-Cre;PtenloxP/loxP mouse model increases collagen fiber number and fiber size within the mammary gland. Pten knockout additionally upregulated Sparc transcription in fibroblasts and promoted collagen shuttling out of the cell. Interestingly, SPARC mRNA expression was observed to be significantly elevated in the tumor stroma as compared to the normal breast in several patient cohorts. While SPARC knockdown via shRNA did not affect collagen shuttling, it notably decreased assembly of exogenous collagen. In addition, SPARC knockdown decreased fibronectin assembly and alignment of the extracellular matrix in an in vitro fibroblast-derived matrix model. Overall, these data indicate upregulation of SPARC is a mechanism by which PTEN regulates collagen deposition in the mammary gland stroma.
Topics: Animals; Cell Line; Collagen; Extracellular Matrix; Fibroblasts; Humans; Mammary Glands, Human; Mice; Mice, Knockout; Osteonectin; PTEN Phosphohydrolase
PubMed: 33534863
DOI: 10.1371/journal.pone.0245653 -
International Immunopharmacology May 2024Inflammation and atherosclerosis (AS) are closely associated to Secreted Protein Acidic and Rich in Cysteine (SPARC) and its related factors. This study attempted to...
BACKGROUND AND AIMS
Inflammation and atherosclerosis (AS) are closely associated to Secreted Protein Acidic and Rich in Cysteine (SPARC) and its related factors. This study attempted to define the role and the potential mechanism of SPARC and its related factors in ameliorating hyperlipidemia and AS by aerobic exercise intervention.
METHODS
The AS rat model was established with a high-fat diet plus vitamin D3 intraperitoneal injection. Treadmill exercises training (5 days/week at 14 m/min for 60 min/day) for 6 weeks was carried out for AS rat intervention method. Western blotting and qRT-PCR were used to analyze the mRNA and protein expression of SPARC and its related factors, respectively. H&E staining was applied to evaluate the morphological changes and inflammation damage. Von Kossa staining was used to measure the degree of vascular calcification. Fluorescence immunohistochemistry staining was used to detect the expression and distribution of SPARC signal molecules.
RESULTS
SPARC was highly expressed and co-localization with the smooth muscle marker α-SMC in the AS rat. And its downstream factors, NF-κB, Caspase-1, IL-1β and IL-18 were upregulated (P < 0.05 or P < 0.01), FNDC5 expression was downregulated in AS rat model. However, slight declined body weight, delayed AS progression, decreased hyperlipidemia and favorable morphology of skeletal muscle and blood vessels have been detected in AS rat with aerobic exercise intervention. Moreover, the expression of SPARC and its downstream factors were decreased (P < 0.05 or P < 0.01), while elevated the expression of FNDC5 (P < 0.01) was observed after aerobic exercise intervention.
CONCLUSIONS
This study suggested that aerobic exercise ameliorated hyperlipidemia and AS by effectively inhibiting SPARC signal, and vascular smooth muscle cells may contribute greatly to the protection of AS.
Topics: Animals; Osteonectin; Atherosclerosis; Male; Physical Conditioning, Animal; Diet, High-Fat; Rats; Rats, Sprague-Dawley; Signal Transduction; Disease Models, Animal; Hyperlipidemias; Cholecalciferol
PubMed: 38537537
DOI: 10.1016/j.intimp.2024.111856 -
Journal of Bone and Mineral Research :... Sep 1990Matched samples of bone from the lumbar spine and tibia were obtained at autopsy from three adult males who had no known evidence of metabolic bone disease at the time... (Comparative Study)
Comparative Study
Matched samples of bone from the lumbar spine and tibia were obtained at autopsy from three adult males who had no known evidence of metabolic bone disease at the time of their demise. The soluble noncollagenous bone proteins were quantitatively extracted from these samples and assayed for the relative content of two bone-associated proteins, osteocalcin and osteonectin. When compared to trabecular bone, cortical bone had higher levels of osteocalcin and much lower levels of osteonectin. When concentration is expressed per gram of dried bone, the osteocalcin excess in cortical bone ranged from 30- to 32-fold, and the osteonectin excess in trabecular bone ranged from 21- to 47-fold. These differences were significant (P less than 0.01) using analysis of variance. We conclude that the human skeleton is not homogeneous with regard to these biochemical markers and that cortical and trabecular bone are biochemically quite distinct. This implies that these two types of bone may be subject to distinct regulatory mechanisms and that global assessments of skeletal function and bone quality based upon soluble markers should be applied with caution. The data also imply that a differential assessment of skeletal performance may be possible using biochemical serum markers.
Topics: Aged; Bone and Bones; Humans; Male; Middle Aged; Osteocalcin; Osteonectin; Proteins; Radioimmunoassay; Solubility
PubMed: 2281823
DOI: 10.1002/jbmr.5650050906 -
Neuroscience Letters Feb 2021Hevin and secreted protein acidic and rich in cysteine (SPARC) are highly homologous matricellular proteins that function in concert to guide the formation of brain...
Hevin and secreted protein acidic and rich in cysteine (SPARC) are highly homologous matricellular proteins that function in concert to guide the formation of brain synapses. Here, we investigated the role of these glycoproteins in neuromuscular junction (NMJ) maturation, stability, and repair following injury. Hevin and SPARC mRNA levels in developing (postnatal day 9), adult (postnatal days 90 and 120), and injured (fibular nerve crush) skeletal muscles were assessed with qPCR. Muscle fiber size was analyzed in developing (P9) mice lacking SPARC, Hevin, and both SPARC and Hevin. NMJ morphology was assessed in developing (P9), adult (P90) and injured (fibular nerve crush) mice lacking SPARC, Hevin, and both SPARC and Hevin skeletal muscle. Hevin and SPARC are expressed in skeletal muscles and are upregulated following nerve injury. Hevin mice exhibited delayed NMJ and muscle fiber development but displayed normal NMJ morphology in adulthood and accelerated NMJ reinnervation following nerve injury. Mice lacking SPARC displayed normal NMJ and muscle fiber development but exhibited smaller NMJs with fewer acetylcholine receptor islands in adulthood. Further, SPARC deletion did not result in overt changes in NMJ reformation following nerve injury. The combined deletion of Hevin and SPARC had little effect on NMJ phenotypes observed in single knockouts, however deletion of SPARC in combination with Hevin reversed deficiencies in muscle fiber maturation observed in Hevin muscle. These results identify SPARC and Hevin as extracellular matrix proteins with roles in NMJ development and repair.
Topics: Animals; Calcium-Binding Proteins; Cells, Cultured; Extracellular Matrix Proteins; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Myoblasts; Neuromuscular Junction; Osteonectin; Synapses
PubMed: 33493647
DOI: 10.1016/j.neulet.2021.135663 -
The Journal of Clinical Investigation Apr 2000Bone continuously remodels in response to mechanical and physiological stresses, allowing vertebrates to renew bone as adults. Bone remodeling consists of the cycled...
Bone continuously remodels in response to mechanical and physiological stresses, allowing vertebrates to renew bone as adults. Bone remodeling consists of the cycled synthesis and resorption of collagenous and noncollagenous extracellular matrix proteins, and an imbalance in this process can lead to disease states such as osteoporosis, or more rarely, osteopetrosis. There is evidence that the extracellular matrix glycoprotein osteonectin or secreted protein acidic and rich in cysteine (BM-40) may be important in bone remodeling. Osteonectin is abundant in bone and is expressed in areas of active remodeling outside the skeleton. In vitro studies indicate that osteonectin can bind collagen and regulate angiogenesis, metalloproteinase expression, cell proliferation, and cell-matrix interactions. In some osteopenic states, such as osteogenesis imperfecta and selected animal models for bone fragility, osteonectin expression is decreased. To determine the function of osteonectin in bone, we used contact x-ray, histomorphometry, and Northern blot analysis to characterize the skeletal phenotype of osteonectin-null mice. We found that osteonectin-null mice have decreased bone formation and decreased osteoblast and osteoclast surface and number, leading to decreased bone remodeling with a negative bone balance and causing profound osteopenia. These data indicate that osteonectin supports bone remodeling and the maintenance of bone mass in vertebrates.
Topics: Animals; Bone Diseases, Metabolic; Bone Remodeling; Cell Count; Collagenases; Endothelial Growth Factors; Female; Lymphokines; Male; Matrix Metalloproteinase 13; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoblasts; Osteocalcin; Osteoclasts; Osteonectin; Radiography; Spine; Tibia; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 10749571
DOI: 10.1172/JCI7039