digitoxin and Fibrosis

Renal tubule cells can recover after they undergo AKI (acute kidney injury). An incomplete repair of renal tubules can result in progressive fibrotic CKD (chronic kidney disease). Studies have revealed the relationship between tubular epithelial cells and kidney fibrogenesis. However, the underlying mechanism remains unclear. Hippo pathway components were evaluated in complete/incomplete repair of I/R (ischaemia/reperfusion) AKI rat models, HK-2 cells and AKI human renal biopsy samples. We found that the expression levels of the Hippo pathway components changed dynamically during kidney regeneration and fibrogenesis in rat models of I/R-induced AKI and human renal biopsy samples. The transcription cofactor YAP (Yes-associated protein) might be a key effector of renal regeneration and fibrogenesis. Our results showed further that YAP might elicit both beneficial and detrimental effects on I/R AKI. After I/R injury occurred, YAP could promote the repair of the injured epithelia. The constant YAP increase and activation might be related to interstitial fibrosis and abnormal renal tubule differentiation. These results indicate that the proper modulation of the Hippo pathway, specifically the transcription cofactor YAP, during repair might be a potent therapeutic target in AKI-CKD transition after I/R injury.

Topics: Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Adolescent; Adult; Aged; Animals; Apoptosis Regulatory Proteins; Cell Differentiation; Cell Proliferation; Cells, Cultured; Digitoxin; Female; Fibrosis; Gene Knockdown Techniques; Hepatocyte Growth Factor; Humans; Kidney; Male; Middle Aged; Phosphoproteins; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Rats, Sprague-Dawley; Regeneration; Reperfusion Injury; Signal Transduction; Transcription Factors; Up-Regulation; YAP-Signaling Proteins; Young Adult