Transcriptome profiling reveals distinctive traits of retinol metabolism and neonatal parallels in the MRL/MpJ mouse

Abstract

BackgroundThe MRL/MpJ mouse is a laboratory inbred strain known for regenerative abilities which are manifested by scarless closure of ear pinna punch holes. Enhanced healing responses have been reported in other organs. A remarkable feature of the strain is that the adult MRL/MpJ mouse retains several embryonic biochemical characteristics, including increased expression of stem cell markers.ResultsWe explored the transcriptome of the MRL/MpJ mouse in the heart, liver, spleen, bone marrow and ears. We used two reference strains, thus increasing the chances to discover the genes responsible for the exceptional properties of the regenerative strain. We revealed several distinctive characteristics of gene expression patterns in the MRL/MpJ mouse, including the repression of immune response genes, the up-regulation of those associated with retinol metabolism and PPAR signalling, as well as differences in expression of the genes engaged in wounding response. Another crucial finding is that the gene expression patterns in the adult MRL/MpJ mouse and murine neonates share a number of parallels, which are also related to immune and wounding response, PPAR pathway, and retinol metabolism.ConclusionsOur results indicate the significance of retinol signalling and neonatal transcriptomic relics as the distinguishing features of the MRL/MpJ mouse. The possibility that retinoids could act as key regulatory molecules in this regeneration model brings important implications for regenerative medicine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2075-2) contains supplementary material, which is available to authorized users.

Early induction of NRF2 antioxidant pathway by RHBDF2 mediates rapid cutaneous wound healing

“…Additionally, induction of keratin 17 in injured skin has been shown to initiate keratinocyte proliferation and migration through the AKT/mTOR signaling pathway (Kim et al, 2006). In MRL healer mice, significant upregulation of keratin genes, including keratin 6, 16, and keratin 17, has been observed during regeneration in both the ear and the digits compared with non-healer C567BL/6J mice (Cheng et al, 2013; Podolak-Popinigis et al, 2015). In line with these findings, keratinocyte stimulation using exogenous keratins has shown promise in the treatment of cutaneous wounds by facilitating rapid re-epithelialization (Davidson et al, 2013; Than et al, 2012).…”

De novo transcriptome analysis of differentially expressed genes in the liver of pampus argenteus under temperature stress

“…Retinol is a form of vitamin A, and it is a fat-soluble vitamin; it could be sucked into the inner intestinal epithelial cells with the absorption of fat and mixed into chylomicrons after combining with fatty acid to form an ester and then ingested by the liver by lymph transport. Vitamin A ester is stored in fat-storing cells of the liver and released into the blood when required by the body (Podolak-Popinigis et al 2015). Previous studies have shown that temperature not only has a significant effect on fish growth but can also affect the expression levels of sex steroid hormones in fish, thus affecting gender differentiation (Imsland et al 2007).…”

Enhanced cartilage repair in ‘healer’ mice—New leads in the search for better clinical options for cartilage repair

“…Transcriptomic studies on tissue from healing ear wounds support the notion that the regenerative response in MRL/MpJ mice is associated with an altered inflammatory response [88,89]. A comparison of mRNA expression profiles between MRL/MpJ-Fas lpr (containing a Fas ligand mutation) and C57BL/6 mice revealed that wound repair in the MRL/MpJ mice is associated with a metabolic shift towards a low inflammatory response and increased tissue repair [90].…”

“…A comparison of mRNA expression profiles between MRL/MpJ-Fas lpr (containing a Fas ligand mutation) and C57BL/6 mice revealed that wound repair in the MRL/MpJ mice is associated with a metabolic shift towards a low inflammatory response and increased tissue repair [90]. To gain further insights into tissue-specific differences in gene expression, Podolak-Popinigis et al conducted a transcriptomic analysis on ears and four other tissues from 8-week-old MRL/MpJ and the C57BL/6 and BALB/c reference strains [89]. Pathways analyses indicated MRL/MpJ-specific suppression of immune system genes in all tissues, supporting the hypothesis that immune system regulation is a mechanistically relevant part of the regeneration response.…”