Biology subjects

Kordes, C.

Publications and source records attributed to Kordes, C..

3 recordsLinked to original sources

bioRxiv2025

Human Urine-derived SIX2-positive renal progenitor cells improve kidney injury in an IRI mouse model

Cells with the characteristics of renal progenitor cells are shed in urine. The aim of this study was to investigate whether these SIX2-positive urine-derived renal progenitor cells (UdRPC) have therapeutic potential in treating or managing acute to chronic kidney injuries. Human UdRPC were obtained from a woman aged 35 years, expanded, and characterized in vitro and finally transplanted unilaterally under the renal capsule of mouse kidneys that had undergone ischemia reperfusion injury (IRI). Analyses of blood serum from the mice revealed that the transplanted human UdRPC transiently influenced the secretome of the animals by triggering the release of inflammatory and angiogenic factors. Of obvious therapeutic relevance, however, was the finding that the transplanted cells suppressed renal fibrosis resulting from IRI. The expression of genes linked to inflammation and chronic kidney disease was also reduced in mouse kidneys in the presence of UdRPC. Ultimately, the human UdRPC were able to alleviate the severity of the injury through the amelioration of fibrosis but were unable to restore complete kidney function within 21 days. Nevertheless, the findings of this study demonstrate a significant influence of transplanted UdRPC on kidney fibrosis after acute to chronic injury presumably via an altered secretome.

cell biology↗

bioRxiv2023

Differential modulation of miR-122 transcription by TGFbeta1/BMP6: implications for nonresolving inflammation and hepatocarcinogenesis

Chronic inflammation is widely recognized as a significant factor that promotes and worsens the development of malignancies, including hepatocellular carcinoma. This study aimed to explore the potential role of microRNAs in inflammation-associated nonresolving hepatocarcinogenesis. By conducting a comprehensive analysis of altered microRNAs in animal models with liver cancer of various etiologies, we identified miR-122 as the most significantly downregulated microRNA in the liver of animals with inflammation-associated liver cancer. Although previous research has indicated the importance of miR-122 in maintaining hepatocyte function, its specific role as either the trigger or the consequence of underlying diseases remains unclear. Through extensive analysis of animals and in vitro models, we have successfully demonstrated that MIR122 transcription is differentially regulated by the immunoregulatory cytokines by the transforming growth factor-beta 1 (TGF{beta}1) and the bone morphogenetic protein- 6 (BMP6). Furthermore, we presented convincing evidence directly linking reduced MIR122 transcription to inflammation and in chronic liver diseases. The results of this study strongly suggest that prolonged activation of signaling pathways, leading to disruption of cytokine-mediated regulation of MIR122, may significantly contribute to the onset and exacerbation of chronic liver disease.

cancer biology↗

bioRxiv2023

An optimized workflow for analyzing extracellular vesicles as biomarkers in liver diseases.

Background & AimsExtracellular vesicles (EVs) play an important role in intercellular communication, serving as vehicles for the exchange of biological materials and being involved in the regulation of physiological processes. EVs and their associated cargoes are considered a promising source of disease-associated biomarkers. The purpose of this study was to establish an easy-to-use, reproducible, and scalable workflow to efficiently analyze EVs in the context of liver disease. MethodsAn optimized workflow was established for the pre-analytical processing and isolation of EVs from plasma and serum. Nanoparticle Tracking Analysis (NTA) was used to characterize circulating EVs in the serum of patients with nonalcoholic fatty liver disease (NAFLD), autoimmune liver disease (AIH), and animal models with impaired liver function. EVs were separated from soluble proteins by an optimized, polyethylene glycol (PEG)-based enrichment protocol. Enriched EVs were either labeled and functionally characterized by monitoring cellular uptake or lysed for biomarker identification. ResultsCirculating EVs in the serum of patients with NAFLD or AIH and in different animal models have been characterized by NTA. Here we show that both the quantity and size of EVs in the serum of patients/animal models are significantly different from those of healthy individuals. We show that isolated EVs are functional, and their uptake by acceptor cells can be quantified after fluorescence labelling. Enriched EVs were directly used to analyze RNA biomarkers. Several microRNAs, including miR-15b, -16, -21, -122 and -223, were found to be significantly up-regulated in EVs isolated from the sera of patients with NAFLD and AIH. We show that EVs transport cytokines, and that IL-2, IL-6 and IL-8 were significantly up-regulated in EVs enriched from patients with cholangiocarcinoma (CCA) compared to healthy controls. ConclusionsThe workflow presented here represents an accessible and easy-to-use approach that enables the analysis and enrichment of EVs from complex biological fluids and their preparation for functional characterization or downstream analysis. In this study, the levels of several miRNAs were found to be significantly increased in EVs isolated from AIH and NAFLD patients compared with healthy controls. HighlightsO_LIEVs circulating in crude serum reflect the diseased stage of the donors. C_LIO_LIEnrichment of EVs with the approach presented here efficiently separates soluble proteins from EVs, providing optimal material for further characterization. C_LIO_LIExosomal markers are present in the EVs-enriched fraction. C_LIO_LIEnriched EVs are intact and are functionally taken up by acceptor cells. C_LIO_LIEnriched EVs are suitable, and have been used for, biomarkers identification both at RNA and protein level. C_LI

molecular biology↗