Regulation of cardiomyocyte hypertrophy through dynamic regulation of type I collagen
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE204724 | GEO | 2023/09/15
REPOSITORIES: GEO
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Project description:Regulation of cardiomyocyte hypertrophy through dynamic regulation of type I collagen
| PRJNA842011 | ENA
Project description:The ability of the heart to adapt to increased stress is dependent on the modification of its extracellular matrix (ECM) architecture that is established during postnatal development as cardiomyocytes differentiate, a process that is poorly understood. We hypothesized that the small leucine-rich proteoglycan (SLRP) lumican (LUM), which binds collagen and facilitates collagen assembly in other tissues, may play a critical role in establishing the postnatal murine myocardial ECM. Although previous studies suggest that LUM deficient mice (lum(-/-)) exhibit skin anomalies consistent with Ehlers-Danlos syndrome, lum(-/-) hearts have not been evaluated. These studies show that LUM was immunolocalized to non-cardiomyocytes of the cardiac ventricles and its expression increased throughout development. Lumican deficiency resulted in significant (50%) perinatal death and further examination of the lum(-/-) neonatal hearts revealed an increase in myocardial tissue without a significant increase in cell proliferation. However cardiomyocytes from surviving postnatal day 0 (P0), 1 month (1 mo) and adult (4 mo) lum(-/-) hearts were significantly larger than their wild type (WT) littermates. Immunohistochemistry revealed that the increased cardiomyocyte size in the lum(-/-) hearts correlated with alteration of the cardiomyocyte pericellular ECM components collagen?1(I) and the class I SLRP decorin (DCN). Western blot analysis demonstrated that the ratio of glycosaminoglycan (GAG) decorated DCN to core DCN was reduced in P0 and 1 mo lum(-/-) hearts. There was also a reduction in the ? and ? forms of collagen?1(I) in lum(-/-) hearts. While the total insoluble collagen content was significantly reduced, the fibril size was increased in lum(-/-) hearts, indicating that LUM may play a role in collagen fiber stability and lateral fibril assembly. These results suggest that LUM controls cardiomyocyte growth by regulating the pericellular ECM and also indicates that LUM may coordinate multiple factors of collagen assembly in the murine heart. Further investigation into the role of LUM may yield novel therapeutic targets and/or biomarkers for patients with cardiovascular disease.
| S-EPMC4468017 | biostudies-other
Project description:Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics to investigate collagen fiber production with collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of high-density collagen in pCAVS. Proteomic analysis reported specific collagen peptides are modified by hydroxylated prolines (HYP), a post-translational modification critical to stabilizing the collagen triple helix. Quantitative data analysis reported significant regulation of collagen HYP sites across patient categories. Non-collagen type ECM proteins identified (26/44; 59%) have direct interactions in collagen synthesis, regulation, or modification. Network analysis identified BAMBI (BMP and Activin Membrane Bound Inhibitor) as a potential upstream regulator of the collagen interactome. This is the first study to detail the collagen types and HYP modifications associated with human AV development and pCAVS. We anticipate that this study will inform new therapeutic avenues that inhibit valvular degradation in pCAVS and engineered options for valve replacement.
2021-09-09 | PXD021990 | Pride
Project description:Hypoxia-inducible factor-1 alpha (HIF-1α) is a central transcriptional regulator of hypoxic response. The present study was designed to investigate the role of HIF-1α in mild hypoxia-induced cardiomyocytes hypertrophy and its underlying mechanism. Mild hypoxia (MH, 10% O(2)) caused hypertrophy in cultured neonatal rat cardiac myocytes, which was accompanied with increase of HIF-1α mRNA and accumulation of HIF-1α protein in nuclei. Transient receptor potential canonical (TRPC) channels including TRPC3 and TRPC6, except for TRPC1, were increased, and Ca(2+)-calcineurin signals were also enhanced in a time-dependent manner under MH condition. MH-induced cardiomyocytes hypertrophy, TRPC up-regulation and enhanced Ca(2+)-calcineurin signals were inhibited by an HIF-1α specific blocker, SC205346 (30 μM), whereas promoted by HIF-1α overexpression. Electrophysiological voltage-clamp demonstrated that DAG analogue, OAG (30 μM), induced TRPC current by as much as 170% in neonatal rat cardiomyocytes overexpressing HIF-1α compared to negative control. These results implicate that HIF-1α plays a key role in development of cardiac hypertrophy in responses to hypoxic stress. Its mechanism is associated with up-regulating TRPC3, TRPC6 expression, activating TRPC current and subsequently leading to enhanced Ca(2+)-calcineurin signals.
| S-EPMC3822973 | biostudies-literature
Project description:An alternative promoter of the PGC-1alpha gene gives rise to three new PGC-1alpha isoforms refered to as PGC-1a2 (A2), PGC-1a3 (A3) and PGC-1a4 (A4). The proximal PGC-1 alpha promotor transcribes the canonical PGC-1 alpha which is refered to as PGC-1a1 (A1).G1/G2/G3 samples refer to the Green fluorescent protein (GFP) control samples used in this experiment. Forced expression of the PGC-1a4 isoform results in muslce hypertrophy associated with increased IGF-1 signaling and repression of myostatin signaling.
2012-12-04 | GSE42473 | GEO
Project description:Collagen, a major component of the extracellular matrix, is significantly upregulated in colorectal liver metastasis (CRLM) compared to liver tissue. Expression levels of specific collagen types in CRLM resemble those in colorectal cancer (CRC) and colon tissue. We investigated whether the collagen hydroxylation pattern from the primary tumor also migrates with the metastatic tumor. The degree of collagen alpha-1(I) hydroxylation in colon, CRC, liver, and CRLM tissue in the same individuals (n=14) was studied with mass spectrometry. The degree of hydroxylation was investigated in 36 collagen alpha-1(I) peptides, which covered 54% of the triple helical region. The average degree of hydroxylation in liver tissue was similar to that in colon tissue. The overall degree of hydroxylation was significantly lower (9% +/- 14%) in CRC tissue and also significantly lower (12% +/-22%) in CRLM tissue compared to colon or liver tissue. Still, in previous research of liver and CRLM enzymes involved in collagen hydroxylation were found to be upregulated, whereas P4HB (4-prolyl hydroxylase beta unit) was downregulated. Furthermore, 11 peptides are present with a specific number of hydroxylations that are significantly different between CRLM and liver tissue; these peptides could be candidates for the detection of CRLM. For one of these eleven peptides, a matching naturally occurring peptide in urine has been identified as being significantly different between patients suffering from CRLM and healthy controls. We conclude that the degree of hydroxylation in CRC and CRLM tumor tissue is in general significantly downregulated in comparison to healthy colon and liver tissue. The hydroxylation pattern in CRLM resemble partly the pattern in liver, primary colorectal cancer and colon.
2020-09-16 | PXD015015 | Pride
Project description:Zooarchaeology by Mass Spectrometry (ZooMS) is a rapidly developing and increasingly utilised peptide mass fingerprinting (PMF) technique that analyses Collagen 1A1 and 1A2 marker peptides for the genus- or species-level identification of fragmentary bones in the archaeological record. Traditionally, this analysis is performed using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-ToF-MS) to identify characteristic m/z values of known marker peptides. Here we present data on the application of a modified ZooMS approach, using nanoflow liquid chromatography – tandem mass spectrometry proteomics, to the analysis of a collection of six early colonial Australian (early to mid-19th Century CE) bone artefacts excavated from a site in Pyrmont, Sydney, Australia in 2017. We were successfully able to identify characteristic marker peptides for bovine COL1A1 and COL1A2 in all six artefacts.
2023-11-29 | PXD032926 | Pride
Project description:Astrocyte diversity is greatly influenced by local environmental modulation. In this study, we analyzed the impact of ciliary deficient astrocytes on astrocytes’ intercellular communications and neuronal transcriptomes in the brain. Our analysis revealed a broad disturbance of astrocyte intercellular connectomes and profound changes in neuronal transcriptomic profiles induced by ciliary deficiency in astrocytes.
2024-01-24 | GSE253642 | GEO
Project description:We have previously shown that dysbindin is a potent inducer of cardiomyocyte hypertrophy via activation of Rho-dependent serum-response factor (SRF) signaling. We have now performed a yeast two-hybrid screen using dysbindin as bait against a cardiac cDNA library to identify the cardiac dysbindin interactome. Among several putative binding proteins, we identified tripartite motif-containing protein 24 (TRIM24) and confirmed this interaction by co-immunoprecipitation and co-immunostaining. Another tripartite motif (TRIM) family protein, TRIM32, has been reported earlier as an E3 ubiquitin ligase for dysbindin in skeletal muscle. Consistently, we found that TRIM32 also degraded dysbindin in neonatal rat ventricular cardiomyocytes as well. Surprisingly, however, TRIM24 did not promote dysbindin decay but rather protected dysbindin against degradation by TRIM32. Correspondingly, TRIM32 attenuated the activation of SRF signaling and hypertrophy due to dysbindin, whereas TRIM24 promoted these effects in neonatal rat ventricular cardiomyocytes. This study also implies that TRIM32 is a key regulator of cell viability and apoptosis in cardiomyocytes via simultaneous activation of p53 and caspase-3/-7 and inhibition of X-linked inhibitor of apoptosis. In conclusion, we provide here a novel mechanism of post-translational regulation of dysbindin and hypertrophy via TRIM24 and TRIM32 and show the importance of TRIM32 in cardiomyocyte apoptosis in vitro.
| S-EPMC5473223 | biostudies-literature
Project description:An alternative promoter of the PGC-1 alpha gene gives arrise to 3 new isofroms of the PGC-1 alpha gene refered to as PGC-1a2 (A2), PGC-1a3 (A3) and PGC-1a4 (A4). The proximal PGC-1 alpha promotor transcribes the canonical PGC-1 alpha which is refered to as PGC-1a1 (A1).G1/G2/G3 samples refer to the Green fluorescent protein (GFP) control samples used in this experiment. Forced expression of specifically PGC-1a4 isoform results in muslce hypertrophy associated with increased IGF-1 signaling and repression of myostatin signaling. Adnoviral over expression assays were performed on primary myoblasts from C57BL/6 mice for each of the PGC-1 alpha isoforms originating from the proximal or alternative promotor.
2012-12-04 | E-GEOD-42473 | biostudies-arrayexpress