Background: Chronic hypoxia-induced epithelial-to-mesenchymal transition (EMT) is a crucial process in renal fibrogenesis. Egr-1, as a transcription factor, has been proven to be important in promoting EMT. However, whether it functions in hypoxia-induced renal tubular EMT has not been fully elucidated. Methods: Egr-1 were detected at mRNA and protein levels by qPCR and Western blot analysis respectively after renal epithelial cells were subjected to hypoxia treatment. Meanwhile, EMT phenotype was also observed through identification of relevant EMT-specific markers. siRNA was used to knock down Egr-1 expression and subsequent changes were observed. Specific PKC and MAPK/ERK inhibitors were employed to determine the molecular signaling pathway involved in Egr-1-mediated EMT phenotype. In vivo assays using rat remnant kidney model were used to validate the in vitro results. Furthermore, Egr-1 expression was examined in the samples of CKD patients with the clinical relevance revealed. Results: Hypoxia treatment enhanced the mRNA and protein levels of Egr-1 in HK-2 cells, which was accompanied by a reduced expression of the epithelial marker E-cadherin and an enhanced expression of the mesenchymal marker Fsp-1. Downregulation of Egr-1 with siRNA reversed hypoxia-induced EMT. Using the specific inhibitors to protein kinase C (calphostin C) or MAPK/ERK (PD98059), we identified that hypoxia induced Egr-1 expression through the PKC/ERK pathway. In addition, the upregulation of Egr-1 raised endogenous Snail levels, and the downregulation of Snail inhibited Egr-1-mediated EMT in HK-2 cells. Through in vivo assays using rat remnant kidney and CKD patients' kidney tissues, we found that Egr-1 and Snail were overexpressed in tubular epithelial cells with EMT. Conclusion: Egr-1 may be an important regulator of the development of renal tubular EMT induced by hypoxia through the PKC/ERK pathway and the activation of Snail. Targeting Egr-1 expression or activity might be a novel therapeutic strategy to control renal fibrosis.

Skin epidermal stem cells (SESCs), which share a single origin with corneal epithelial cells (CECs), are considered to be one of the most ideal seed cells for the construction of tissue engineered corneas. However, the mechanism underlying the transdifferentiation of SESCs to CECs has not been fully elucidated. In the present study, to identify critical microRNAs (miRNAs/miRs) and genes that regulate the transdifferentiation of SESCs to CECs, SESCs and CECs were collected from sheep and used for small RNA sequencing and mRNA microarray analyses. Among the differentially expressed miRNAs and genes, 36 miRNAs were downregulated and 123 genes were upregulated in the CECs compared with those in the SESCs. miR-10b exhibited the largest change in expression between the cell types. Target genes of the 36 downregulated miRNAs were predicted and a computational approach demonstrated that these target genes may be involved in several signaling pathways, including the 'PI3K signaling pathway', the 'Wnt signaling pathway' and the 'MAPK signaling pathway', as well as in 'focal adhesion'. Comparison of these target genes to the 123 upregulated genes identified 43 intersection genes. A regulatory network of these 43 intersection genes and its correlative miRNAs were constructed, and three genes (dedicator of cytokinesis 9, neuronal differentiation 1 and activated leukocyte cell adhesion molecule) were found to have high interaction frequencies. The expression levels of 7 randomly selected miRNAs and the 3 intersection genes were further validated by reverse transcription-quantitative polymerase chain reaction. It was found that miR-10b, the Wnt signaling pathway and the 3 intersection genes may act together and serve a critical role in the transdifferentiation process. This study identified miRNAs and genes that were expressed in SESCs and CECs that may assist in uncovering its underlying molecular mechanism, as well as promote corneal tissue engineering using epidermal stem cells for clinical applications.

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The Chinese giant salamander (Andrias davidianus) has been increasingly popular in the aquaculture market in China in recent years. In the breeding process of Andrias davidianus, we found that some albino individuals were extremely rare and could not be inherited stably, which severely limits their commercialization in the aquaculture market. In this study, we performed transcriptome and small RNA (sRNA) sequencing analyses in the skin samples of wild-type (WT) and albino (AL) Andrias davidianus. In total, among 5517 differentially expressed genes (DEGs), 2911 DEGs were down-regulated in AL, including almost all the key genes involved in melanin formation. A total of 25 miRNAs were differentially expressed in AL compared to WT, of which 17 were up-regulated. Through the integrated analysis, no intersection was found between the target genes of the differentially expressed miRNAs and the key genes for melanin formation. Gene Ontology (GO) and KEGG pathway analyses on DEGs showed that these genes involved multiple processes relevant to melanin synthesis and the key signal pathway MAPK. Interestingly, the transcription factors SOX10 and PAX3 and the Wnt signaling pathway that play a key role in other species were not included, while the other two transcription factors in the SOX family, SOX21 and SOX7, were included. After analyzing the key genes for melanin formation, it was interesting to note an alternative splicing form of the MITF in WT and a critical mutation of the SLC24A5 gene in AL, which might be the main reason for the skin color change of Andrias davidianus. The results contributed to understanding the molecular mechanism of skin pigmentation in Andrias davidianus and accelerating the acquisition process of individuals with specific body colors by genetic means.

Accumulating evidence has shown that cell dedifferentiation or reprogramming is a pivotal procedure for animals to deal with injury and promote endogenous tissue repair. Tissue damage is a critical factor that triggers cell dedifferentiation or reprogramming in vivo. By contrast, microenvironmental changes, including the loss of stem cells, hypoxia, cell senescence, inflammation and immunity, caused by tissue damage can return cells to an unstable state. If the wound persists in the long-term due to chronic damage, then dedifferentiation or reprogramming of the surrounding cells may lead to carcinogenesis. In recent years, extensive research has been performed investigating cell dedifferentiation or reprogramming in vivo, which can have significant implications for wound repair, treatment and prevention of cancer in the future. The current review summarizes the molecular events that are known to drive cell dedifferentiation directly following tissue injury and the effects of epigenetic modification on dedifferentiation or reprogramming in vivo. In addition, the present review explores the intracellular mechanism of endogenous tissue repair and its relationship with cancer, which is essential for balancing the risk between tissue repair and malignant transformation after injury.