Organ fibrosis is a process in which cellular homeostasis is disrupted and extracellular matrix is excessively deposited. Fibrosis can lead to vital organ failure and there are no effective treatments yet. Although epithelial–mesenchymal transition (EMT) may be one of the key cellular mechanisms, the underlying mechanisms of fibrosis remain largely unknown. EMT is a cell phenotypic process in which epithelial cells lose their cell-to-cell adhesion and polarization, after which they acquire mesenchymal features such as infiltration and migration ability. Upon injurious stimulation in different organs, EMT can be triggered by multiple signaling pathways and is also regulated by epigenetic mechanisms. This narrative review summarizes the current understanding of the underlying mechanisms of EMT in fibrogenesis and discusses potential strategies for attenuating EMT to prevent and/or inhibit fibrosis. Despite better understanding the role of EMT in fibrosis development, targeting EMT and beyond in developing therapeutics to tackle fibrosis is challenging but likely feasible.

Cystinuria is a genetically inherited disorder of renal and intestinal transport, featured as a high concentration of cystine in the urine. Cumulative cystine in urine would cause the formation of kidney stones, which further leads to renal colic and dysfunction. Gene screens have found that mutations in SLC3A1 or SLC7A9 gene are responsible for most cases of cystinuria, for encoding defective cystine transporters. Here, we presented the genotypic and phenotypic characteristics of one unique case of a three-generation Chinese family. The proband developed severe urolithiasis combined with renal damage. The radiography and computed tomography (CT) scan showed calculus in the left pelvic kidney. Postoperative stone analysis revealed that the stones were mainly composed of cystine. Therefore, to explore its pathogenesis, next-generation Whole Exome Sequencing (WES) and Sanger sequencing identify the proband mutated gene of the proband’s family. In this article, we reported novel compound heterozygous mutations (c.818G>A and c.1011G>A) of the SLC3A1 gene in a 5-year-old child suffering from a cystine stone from a three-generation family. Bioinformatic analysis was used to predict the pathogenicity and conservation of the target mutation. Conservative sequence and evolutionary conservation analysis indicated that cystine273 and proline337 were highly conserved among species, and both mutations listed here (Cys273Tyr and Pro337Pro) were pathogenic. To conclude, our study expands the phenotypic and genotypic spectrum of SLC3A1 and indicates that genetic screening should be considered in the clinic to provide more effective and precise treatment for cystinuria.