Interleukin-1α dependent survival of cardiac fibroblasts is associated with StAR/STARD1 expression and improved cardiac remodeling and function after myocardial infarction

Razin, Talya; Melamed-Book, Naomi; Argaman, Jasmin; Galin, Iris; Lowy, Yosef; Anuka, Eli; Naftali‐Shani, Nili; Kandel-Kfir, Michal; Garfinkel, Benjamin P.; Brielle, Shlomi; Granot, Zvi; Apte, Ron N.; Conway, Simon J.; Molkentin, Jeffery D.; Kamari, Yehuda; Leor, Jonathan; Orly, Joseph

doi:10.1016/j.yjmcc.2020.10.013

“…19 IL1A (Interleukin 1 Alpha) is related to cytokine activity and interleukin-1 receptor binding and its associated pathways are IL1α-NF-κB pathway and cytokine signaling in Immune system. [20][21][22] As shown Figure 1A, those two genes (CDKN2A and IL1A) are closely associated with the progress of cell senescence. MAP2K1 is Mitogen-Activated Protein Kinase Kinase 1, which is related to pathways of apoptosis and survival anti-apoptoticaction 23,24 .…”

Section: Discussionmentioning

confidence: 90%

“…Among its associated pathways are DNA Damage Response and Mitotic G1‐G1/S phases 19 . IL1A (Interleukin 1 Alpha) is related to cytokine activity and interleukin‐1 receptor binding and its associated pathways are IL1α‐NF‐κB pathway and cytokine signaling in Immune system 20–22 . As shown Figure 1A, those two genes (CDKN2A and IL1A) are closely associated with the progress of cell senescence.…”

Section: Discussionmentioning

confidence: 99%

Identification of several senescence‐associated genes signature in head and neck squamous cell carcinoma

Wang

¹

,

Zhou

²

,

Sun

³

et al. 2022

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Background As one of the core aging processes, cellular senescence is associated with tumorigenesis, growth, and immune modulation in cancers. Nevertheless, the prognosis of senescence‐associated genes (SAGs) signature in head and neck squamous cell carcinoma (HNSCC) remains to be further evaluated. Methods The transcriptome and corresponding clinical datasets of SAGs in patients with HNSCC were downloaded from public databases. A new prognostic SAGs signature was established with least absolute shrinkage and selection operator discussion. Patients with HNSCC were fallen into two risk groups based on each sample's risk mark and the cutoff point. The survival analysis was extended to determine the predictive accuracy of the SAGs signature. Furthermore, the evaluation of SAGs signature was made according to clinicopathological characteristics, survival state, the infiltration of inflammatory cells, and efficacy of immunotherapy. Results 41 SAGs were recognized and adopted to establish the forecast signature. The survival analysis indicated that patients with HNSCC in the high‐senescent score group had significantly reduced overall survival compared with those in the low‐senescent score group. It was certified that the risk score of SAGs signature was a separate predicting agent for HNSCC applying Cox regression analysis. According to functional analysis, some immune‐associated pathways were increased in the low‐senescent score group significantly. High‐senescent score group was correlated with poor clinicopathological characteristics, given less the infiltration of inflammatory cells state and worse immunotherapeutic effect. Conclusion A new SAG signature predicting result and response to immunotherapy of HNSCC was identified. Cellular senescence may be a hidden target for HNSCC.

show abstract

“…By measuring the level of the Postn gene rather than that of its protein in the tissue, we were able to exclude periostin that had accumulated in the ECM [27] and narrow the results to include only the periostin during its synthesis by cells to obtain a more accurate report. We found that periostin mRNA expression in the infarction region of C57Bl/6J mice increased signi cantly during days 4-7 after the MI and decreased on day 14.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, therefore, we aimed to elucidate the timeline of periostin expression after MI to maximize the treatment effects of time-based periostin manipulation. The present paper describes the limited period after MI during which periostin is produced in cardiac brosis by focusing on the levels of the periostin gene and its protein in the cell, where periostin is originally produced, rather than quantifying its levels in tissues [23,27], which could result in an inaccurate estimate. In this study, C57BL6J and BALB/c mice were subjected to surgical MI via left coronary artery ligation.…”

Section: Introductionmentioning

confidence: 99%

Defining the timeline of periostin upregulation in cardiac fibrosis following acute myocardial infarction in mice

Gil

¹

,

Goldshtein

²

,

Etzion

³

et al. 2022

Preprint

View full text Add to dashboard Cite

After myocardial infarction (MI), the heart's reparative response to the ischemic insult and the related loss of cardiomyocytes involves cardiac fibrosis, in which the damaged tissue is replaced with a fibrous scar. Although the scar is essential to prevent ventricular wall rupture in the infarction zone, it expands over time to remote, non-infarct areas, significantly increasing the extent of fibrosis and markedly altering cardiac structure. Cardiac function in this scenario deteriorates, thereby increasing the probability of heart failure and the risk of death. Recent works have suggested that the matricellular protein periostin, known to be involved in fibrosis, is a candidate therapeutic target for the regulation of MI-induced fibrosis and remodeling. Different strategies for the genetic manipulation of periostin have been proposed previously, yet those works did not properly address the time dependency between periostin activity and cardiac fibrosis. Our study aimed to fill that gap in knowledge and fully elucidate the explicit timing of cellular periostin upregulation in the infarcted heart to enable the safer and more effective post-MI targeting of periostin-producing cells. Surgical MI was performed in C57BL/6J and BALB/c mice by ligation of the left anterior descending coronary artery. Flow cytometry analyses of cells derived from the infarcted hearts and quantitative real-time PCR of the total cellular RNA revealed that periostin expression increased during days 2–7 and peaked on day 7 post-infarct, regardless of mouse strain. The established timeline for cellular periostin expression in the post-MI heart is a significant milestone toward the development of optimal periostin-targeted gene therapy.

show abstract

“…In this study, therefore, we aimed to elucidate the timeline of periostin expression after MI to maximize the treatment effects of time-based periostin manipulation. The present paper describes the limited period after MI during which periostin is produced by focusing on the levels of the periostin gene and its protein in the cell , where periostin is originally produced, rather than quantifying its levels in tissues 22 , which could result in an inaccurate estimate. In this study, C57BL6J and BALB/c mice were subjected to surgical MI via left coronary artery ligation.…”

Section: Introductionmentioning

confidence: 99%

Defining the timeline of periostin upregulation in cardiac fibrosis following acute myocardial infarction in mice

Gil

¹

,

Goldshtein

²

,

Etzion

³

et al. 2022

Sci Rep

View full text Add to dashboard Cite

After myocardial infarction (MI), the heart's reparative response to the ischemic insult and the related loss of cardiomyocytes involves cardiac fibrosis, in which the damaged tissue is replaced with a fibrous scar. Although the scar is essential to prevent ventricular wall rupture in the infarction zone, it expands over time to remote, non-infarct areas, significantly increasing the extent of fibrosis and markedly altering cardiac structure. Cardiac function in this scenario deteriorates, thereby increasing the probability of heart failure and the risk of death. Recent works have suggested that the matricellular protein periostin, known to be involved in fibrosis, is a candidate therapeutic target for the regulation of MI-induced fibrosis and remodeling. Different strategies for the genetic manipulation of periostin have been proposed previously, yet those works did not properly address the time dependency between periostin activity and cardiac fibrosis. Our study aimed to fill that gap in knowledge and fully elucidate the explicit timing of cellular periostin upregulation in the infarcted heart to enable the safer and more effective post-MI targeting of periostin-producing cells. Surgical MI was performed in C57BL/6J and BALB/c mice by ligation of the left anterior descending coronary artery. Flow cytometry analyses of cells derived from the infarcted hearts and quantitative real-time PCR of the total cellular RNA revealed that periostin expression increased during days 2–7 and peaked on day 7 post-infarct, regardless of mouse strain. The established timeline for cellular periostin expression in the post-MI heart is a significant milestone toward the development of optimal periostin-targeted gene therapy.

show abstract

Interleukin-1α dependent survival of cardiac fibroblasts is associated with StAR/STARD1 expression and improved cardiac remodeling and function after myocardial infarction

Cited by 9 publications

References 68 publications

Identification of several senescence‐associated genes signature in head and neck squamous cell carcinoma

Identification of several senescence‐associated genes signature in head and neck squamous cell carcinoma

Defining the timeline of periostin upregulation in cardiac fibrosis following acute myocardial infarction in mice

Defining the timeline of periostin upregulation in cardiac fibrosis following acute myocardial infarction in mice

Contact Info

Product

Resources

About