Transforming growth factor-beta and Forkhead box O transcription factors as cardiac fibroblast regulators

Norambuena-Soto, Ignacio; Núñez-Soto, Constanza; Sanhueza–Olivares, Fernanda; Cancino-Arenas, Nicole; Mondaca‐Ruff, David; Vivar, Raúl; Díaz‐Araya, Guillermo; Mellado, Rosemarie; Chiong, Mario

doi:10.5582/bst.2017.01017

Cited by 21 publications

(12 citation statements)

References 90 publications

(97 reference statements)

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“…Others have reported that FOXO1 and FOXO3 were upregulated in skin wound healing of mice, and the partial knockout of FOXO1 in mice led to accelerated wound healing and reduced scar formation . More to the point, the activation of cardiomyofibroblasts and the onset of cardiac fibrosis in heart pathologies have been associated with noncanonical TGF‐β1 activation of FOXO transcription factors . PTEN‐regulated Akt/FOXO signaling has been studied extensively in cancer and has also been a pathway of interest in fibrosis .…”

Section: Discussionmentioning

confidence: 99%

“…25 More to the point, the activation of cardiomyofibroblasts and the onset of cardiac fibrosis in heart pathologies have been associated with noncanonical TGF-β1 activation of FOXO transcription factors. 26 PTEN-regulated Akt/FOXO signaling has been studied extensively in cancer 27 and has also been a pathway of interest in fibrosis. 28 The observed coupling of the activation/inhibition of FOXO1-and Mycrelated processes could be interesting since there are numerous reports associating Myc with the promotion of renal fibrosis, 29 liver fibrosis, 30 and chronic skin wounds and scarring.…”

Section: Discussionmentioning

confidence: 99%

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Transcriptomic Analysis of Cellular Pathways in Healing Flexor Tendons of Plasminogen Activator Inhibitor 1 (PAI‐1/Serpine1) Null Mice

Freeberg

Easa

Lillis

et al. 2019

Journal Orthopaedic Research

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Injuries to flexor tendons can be complicated by fibrotic adhesions, which severely impair the function of the hand. Plasminogen activator inhibitor 1 (PAI‐1/SERPINE1), a master suppressor of fibrinolysis and protease activity, is associated with adhesions. Here, we used next‐generation RNA sequencing (RNA‐Seq) to assess genome‐wide differences in messenger RNA expression due to PAI‐1 deficiency after zone II flexor tendon injury. We used the ingenuity pathway analysis to characterize molecular pathways and biological drivers associated with differentially expressed genes (DEG). Analysis of hundreds of overlapping and DEG in PAI‐1 knockout (KO) and wild‐type mice (C57Bl/6J) during tendon healing revealed common and distinct biological processes. Pathway analysis identified cell proliferation, survival, and senescence, as well as chronic inflammation as potential drivers of fibrotic healing and adhesions in injured tendons. Importantly, we identified the activation of PTEN signaling and the inhibition of FOXO1‐associated biological processes as unique transcriptional signatures of the healing tendon in the PAI‐1/Serpine1 KO mice. Further, transcriptomic differences due to the genetic deletion of PAI‐1 were mechanistically linked to PI3K/Akt/mTOR, PKC, and MAPK signaling cascades. These transcriptional observations provide novel insights into the biological roles of PAI‐1 in tendon healing and could identify therapeutic targets to achieve scar‐free regenerative healing of tendons. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:43–58, 2020

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis of Cellular Pathways in Healing Flexor Tendons of Plasminogen Activator Inhibitor 1 (PAI‐1/Serpine1) Null Mice

Freeberg

Easa

Lillis

et al. 2019

Journal Orthopaedic Research

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“…cumulus cell (CCs) expansion includes hyaluronan-rich ECM after an LH surge. Furthermore, successful ovulation requires precise ECM remodeling to ensure follicle rupture [11,[13][14][15][16].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

ADAMTS1 and HSPG2 mRNA levels in cumulus cells are related to human oocyte quality and controlled ovarian hyperstimulation outcomes

Jin

Yang

et al. 2020

J Assist Reprod Genet

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Purpose The study investigated potential correlations between the expression levels of ADAMTS1 and HSPG2 in cumulus cells (CCs) and controlled ovarian hyperstimulation (COH) outcomes. Methods RT-PCR was used to determine ADAMTS1 and HSPG2 mRNA levels in mice CCs at different timepoints (0, 4, 8, 12, and 16 h) after human chorionic gonadotropin (hCG) injection, and in CCs after RNAi treatment. Women with polycystic ovary syndrome (PCOS) (n = 45) and normal ovulatory controls (n = 103) undergoing IVF/ICSI were recruited. Relative ADAMTS1 and HSPG2 mRNA levels were measured by RT-PCR. Moreover, correlations of ADAMTS1 and HSPG2 levels with COH outcomes were analyzed. Results At different timepoints after hCG treatment, ADAMTS1 mRNA had the highest level at 12 h, whereas HSPG2 showed opposite profiles to ADAMTS1 with the lowest level at 12 h. HSPG2 expression was upregulated after ADAMTS1 RNAi treatment The PCOS group had higher HSPG2 and lower ADAMTS1 expression levels than controls. In normal ovulatory women (control group), a higher expression of ADAMTS1 and lower expression of HSPG2 were associated with more mature oocytes, transplantable embryos, and good quality embryos, whereas higher transplantable embryo rates and good quality embryo rates were obtained only with lower HSPG2 expression. ROC curves showed the co-measurement of ADAMTS1 and HSPG2 had a better predictive power than separate analyses. Conclusion The dynamic profiles of ADAMTS1 and HSPG2 were inversely correlated in CCs. In PCOS and normal ovulatory patients, higher ADAMTS1 and lower HSPG2 expression levels in CCs were related to better COH outcomes.

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“…Moreover, TGF-β1 was also stained to explore the effect of CoQ10-LIP+UTMD on anti-fibrosis at kidney. Previous study demonstrated that TGF-β1 played an important role in regulating fibrosis, of which overexpression was liable to induce myocardial fibrosis [ 37 , 38 ]. As shown in Figure 5D , TGF-β1 was highly expressed in kidney of DN rats groups compared with normal group.…”

Section: Resultsmentioning

confidence: 99%

CoQ10-loaded liposomes combined with UTMD prevented early nephropathy of diabetic rats

Chen

Ting-Yue

et al. 2018

Oncotarget

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Nephropathy is one of the most severe complications of diabetic patients. The therapeutic strategies for diabetic patients should not only focus on the control of blood glucose but also pay attention to the occurrence of diabetic nephropathy (DN). Coenzyme Q10 (CoQ10) has great therapeutic potential for DN. However, the clinical application of CoQ10 has been limited because of its low water-solubility and non-specific distribution. Liposomes were supposed to be an effective way for delivering CoQ10 to kidney. CoQ10 was effectively encapsulated into the liposome (CoQ10-LIP) with a high entrapment efficiency of 86.15 %. The CoQ10-LIP exhibited a small hydrodynamic diameter (180 ± 2.1 nm) and negative zeta potential (−18.20 mV). Moreover, CoQ10-LIP was combined with ultrasound-mediated microbubble destruction (UTMD) to enhance specific distribution of CoQ10 in kidney. In early stage of diabetic mellitus (DM), rats were administrated with CoQ10-LIP followed by UTMD (CoQ10-LIP+UTMD) to prevent occurrence of DN. Results revealed that CoQ10-LIP+UTMD effectively prevented the renal morphology and function of diabetics rats from damage. The protective mechanism of CoQ10-LIP was highly associated with protecting podocyte, promoting vascular repair and inhibiting cell apoptosis. Conclusively, CoQ10-LIP in combination with UTMD might be a potential strategy to prevent occurrence of DN.

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Transforming growth factor-beta and Forkhead box O transcription factors as cardiac fibroblast regulators

Cited by 21 publications

References 90 publications

Transcriptomic Analysis of Cellular Pathways in Healing Flexor Tendons of Plasminogen Activator Inhibitor 1 (PAI‐1/Serpine1) Null Mice

Transcriptomic Analysis of Cellular Pathways in Healing Flexor Tendons of Plasminogen Activator Inhibitor 1 (PAI‐1/Serpine1) Null Mice

ADAMTS1 and HSPG2 mRNA levels in cumulus cells are related to human oocyte quality and controlled ovarian hyperstimulation outcomes

CoQ10-loaded liposomes combined with UTMD prevented early nephropathy of diabetic rats

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