Endothelin and hepatic wound healing

Khimji, Al-karim; Rockey, Don C.

doi:10.1016/j.phrs.2011.03.005

Cited by 23 publications

(18 citation statements)

References 117 publications

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“…Importantly, a large body of experimental literature suggests that EDNRA and EDNRB expression correlates with the severity of the disease21, and therapy using an EDN receptor antagonist directed at intervening in the EDN1 signaling pathway had significant therapeutic potential in patients with liver disease22. Given the important role of EDN1 in fibrosis, our present findings at the cellular level suggest that HEM suppresses the EDN1 signaling network via the down-regulation of EDNRA and EDNRB expression, which in turn contributed to the cells' increased resistance to exogenous TGFβ1-stimulated fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Eggshell membrane ameliorates hepatic fibrogenesis in human C3A cells and rats through changes in PPARγ-Endothelin 1 signaling

Jia

Saito

et al. 2014

Sci Rep

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Our previous nutrigenomic findings indicate that eggshell membrane (ESM) may prevent liver fibrosis. Here we investigated the effects and mechanisms underlying ESM intervention against liver injury by using DNA microarray analysis and comparative proteomics. In vitro hydrolyzed ESM attenuated the TGFβ1-induced procollagen production of human hepatocyte C3A cells and inhibited the expression of Endothelin 1 (EDN1) and its two receptors, and extracellular matrix components. In vivo male Wistar rats were allocated into a normal control group, a CCl4 group (hypodermic injection of 50% CCl4 2×/wk) and an ESM group (20 g ESM/kg diet with CCl4 injection) for 7 wks. Dietary ESM ameliorated the elevated activity of ALT/AST, oxidative stress and collagen accumulation in liver, accompanied by the down-regulated expression of Edn1 signaling and notable profibrogenic genes and growth factors as well as peroxisome proliferator-activated receptor gamma (PPARγ). Concomitantly, the decreased expressions of Galectin-1 and Desmin protein in the ESM group indicated the deactivation of hepatic stellate cells (HSCs). Through a multifaceted integrated omics approach, we have demonstrated that ESM can exert an antifibrotic effect by suppressing oxidative stress and promoting collagen degradation by inhibiting HSCs' transformation, potentially via a novel modulation of the PPARγ-Endothelin 1 interaction signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Eggshell membrane ameliorates hepatic fibrogenesis in human C3A cells and rats through changes in PPARγ-Endothelin 1 signaling

Jia

Saito

et al. 2014

Sci Rep

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“…To this end, it is notable that the quality of repair processes in general and, in particular, this of wound healing has not been investigated in FS-affected individuals. However, there is a large number of direct and indirect indications which motivates the healing relevant research to be dedicated specifically to the FS affected individuals, namely -Elevated ET-1 and systemic hypoxia typical for FS and detrimental for WH [75,151] -Retinal vein occlusion is frequently demonstrated by FS individuals [150] -At the molecular level, repair processes are diminished and both MMP-2 and MMP-9 are highly activated in FS individuals as well as in FS-affected patients suffering from normal-tension glaucoma; consequently tissues remodelling is altered in this patient cohort [152,153] -Finally, FS may predispose cancer patients to both impaired wound healing and aggressive metastatic disease, due to systemic hypoxic effects and upregulation of MMPs as proposed by dedicated research [149,[154][155][156].…”

Section: Concluding Remarks Working Hypotheses and Expert Recommendamentioning

confidence: 99%

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

Avishai¹,

2017

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Whereas the physiologic wound healing (WH) successfully proceeds through the clearly defined sequence of the individual phases of wound healing, chronic non-healing wounds/ulcers fail to complete the individual stages and the entire healing process. There are many risk factors both modifiable (such as stress, smoking, inappropriate alcohol consumption, malnutrition, obesity, diabetes, cardio-vascular disease, etc.) and non-modifiable (such as genetic diseases and ageing) strongly contributing to the impaired WH. Current statistics demonstrate that both categories are increasingly presented in the populations, which causes dramatic socio-economic burden to the healthcare sector and society at large. Consequently, innovative concepts by predictive, preventive and personalised medicine are crucial to be implemented in the area. Individual risk factors, causality, functional interrelationships, molecular signature, predictive diagnosis, and primary and secondary prevention are thoroughly analysed followed by the expert recommendations in this paper.

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“…ECE1 also has a role in cleaving Big-EDN to generate an active, secretory EDN1 (Khimji and Rockey, 2011). Thus, we examined the expression of NK1R, ECE1, and EDNs to determine whether they functioned as downstream signaling molecules for SP.…”

Section: Sp Stimulates the Expression Of Pigmentation-related Genesmentioning

confidence: 99%

Substance P Stimulates Endothelin 1 Secretion via Endothelin-Converting Enzyme 1 and Promotes Melanogenesis in Human Melanocytes

Park

Lee

Cho

2015

Journal of Investigative Dermatology

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Substance P (SP) is a well-known neuropeptide implicated in the wound-healing process. The wound occasionally causes a pigmented scar. In the present study, we examined whether increased levels of SP affected melanogenesis. When human melanocytes were treated with SP, the melanin content increased and the pigmentation process accelerated in a dose-dependent manner. In addition to melanogenesis-related genes, the expression of neurokinin 1 receptor, endothelin 1 (EDN1), and EDN receptor type B (EDNRB) also increased at both the messenger RNA and protein levels. Interestingly, secreted EDN1 was observed in the melanocyte culture medium, and this phenomenon was significantly enhanced by SP treatment. Through knockdown experiments using small interfering RNAs (siRNAs), we confirmed that endothelin-converting enzyme 1 (ECE1), EDN1, and EDNRB were involved in SP-induced pigmentation and found that EDN1 secretion was affected by ECE1 and EDN1 siRNAs, but not by EDNRB siRNA. These findings indicate that ECE1 is essential for EDN1 secretion in melanocytes and that EDNRB functions downstream of secreted EDN1 to increase the cAMP levels and activate the melanogenesis-related phosphorylation cascade. This study provides in vitro evidence for a melanogenic function of SP in the skin and suggests that the SP-related signal is a potent target for regulating stress- or wound-induced pigmentation.

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Endothelin and hepatic wound healing

Cited by 23 publications

References 117 publications

Eggshell membrane ameliorates hepatic fibrogenesis in human C3A cells and rats through changes in PPARγ-Endothelin 1 signaling

Eggshell membrane ameliorates hepatic fibrogenesis in human C3A cells and rats through changes in PPARγ-Endothelin 1 signaling

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

Substance P Stimulates Endothelin 1 Secretion via Endothelin-Converting Enzyme 1 and Promotes Melanogenesis in Human Melanocytes

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