Differentiated kidney epithelial cells repair injured proximal tubule

Abstract

Significance When epithelial cells in the proximal portion of the nephron are damaged they rapidly proliferate to repair the damage to the kidney. Whether a stem cell is responsible for this proliferative response or not is controversial. Although a scattered population of cells can be found in the human proximal tubule that seem to have stem-cell characteristics, they could also represent isolated damaged cells that have dedifferentiated and lost their epithelial characteristics. We resolve these conflicting models using genetic lineage analysis to demonstrate that fully differentiated proximal tubule cells not only proliferate after injury, but they also upregulate apparent stem-cell markers. This study shows that epithelial dedifferentiation is responsible for repair of mouse proximal tubule, rather than an adult stem-cell population.

Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both CDK4/6 and OCT2 functions

“…Remarkably, during AKI, the normally quiescent renal tubular cells reenter the cell cycle (29)(30)(31)(32)(33)(34), and blocking cell-cycle progression can reduce renal injury (28). Here, we provide evidence that the CDK4/6 pathway is activated early during AKI and demonstrate significant protective effects of CDK4/6 inhibitors in animal models of cisplatin-induced AKI.…”

“…However, the major etiology of AKI is renal tubular cell death caused by ischemia, infections, or drug-induced toxicities (44)(45)(46)(47). During AKI, along with cell death, cell-cycle activation is initiated in the normally quiescent renal tubular cells (29)(30)(31)(32)(33)(34). It is believed that this proliferative response may contribute to tissue regeneration (28,32,33,38), although this notion has been challenged recently (48).…”

“…During AKI, along with cell death, cell-cycle activation is initiated in the normally quiescent renal tubular cells (29)(30)(31)(32)(33)(34). It is believed that this proliferative response may contribute to tissue regeneration (28,32,33,38), although this notion has been challenged recently (48). These issues notwithstanding, it is clear that a significant fraction of renal tubular cells enter the cell cycle during AKI (32,34) and that blocking or delaying cell-cycle entry has protective effects (28).…”

Dietary myo-inositol modulates immunity through antioxidant activity and the Nrf2 and E2F4/cyclin signalling factors in the head kidney and spleen following infection of juvenile fish with Aeromonas hydrophila

“…In the present study, we observed that MI deficiency down-regulated the Nrf2 mRNA levels, suggesting that the down-regulation of the mRNA levels of antioxidant-related genes (CuZnSOD, MnSOD, CAT, GPx1a and GR) by MI deficiency was at least partially related to the downregulation of Nrf2 gene transcription in the head kidneys and spleens of the fish after challenge with A. hydrophila. Recently, cells were reported to rapidly proliferate to repair kidney damage in mice when cells in the proximal portion of the nephron were damaged [73]. However, if serious damage occurred (especially DNA damage), the cell proliferation could arrest [74].…”

Tubular epithelial C1orf54 mediates protection and recovery from acute kidney injury

“…P38 MAPK, JNK, STAT3, Wnt/β‐catenin and PI3K/AKT signalling pathways were reported to be involved in TEC proliferation11, 12; thus, we examined whether these signalling pathways participate in C1orf54‐mediated TEC proliferation. We found that kidney IRI led to P38, JNK, STAT3 and β‐catenin activation, while deficiency of C1orf54 did not alter phosphorylation of P38, JNK and STAT3, and expression level of β‐catenin (Figure 8A,B), indicating that these signalling pathways were not essential for TEC proliferation.…”