Specific expression of survivin, SOX9, and CD44 in renal tubules in adaptive and maladaptive repair processes after acute kidney injury in rats

Acute kidney injury (AKI) is thought to be a reversible condition; however, growing evidence has suggested that AKI may be associated with subsequent development of chronic kidney disease. Although renal tubules have intrinsic regeneration capacity, disruption of the regeneration mechanisms leads to...

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Veröffentlicht in:Journal of applied toxicology 2021-04, Vol.41 (4), p.607-617
Hauptverfasser: Matsushita, Kohei, Toyoda, Takeshi, Yamada, Takanori, Morikawa, Tomomi, Ogawa, Kumiko
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Sprache:eng
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Zusammenfassung:Acute kidney injury (AKI) is thought to be a reversible condition; however, growing evidence has suggested that AKI may be associated with subsequent development of chronic kidney disease. Although renal tubules have intrinsic regeneration capacity, disruption of the regeneration mechanisms leads to irreversible interstitial fibrosis. In this study, we investigated immunohistochemical markers of renal tubules in adaptive and maladaptive repair processes to predict AKI reversibility. Histopathological analysis demonstrated that regenerative tubules and dilated tubules were observed in the kidneys of AKI model rats after ischemia/reperfusion (I/R). Regenerative tubules gradually redifferentiated after I/R, whereas dilated tubules exhibited no tendency for redifferentiation. In fibrotic areas of the kidney in renal fibrosis model rats subjected to I/R, renal tubules were dilated or atrophied. There results suggested that the histopathological features of renal tubules in the maladaptive repair were dilation or atrophy. From microarray data of regenerative tubules, survivin, SOX9, and CD44 were extracted as candidate markers. Immunohistochemical analysis demonstrated that survivin and SOX9 were expressed in regenerative tubules, whereas SOX9 was also detected in renal tubules in fibrotic areas. These findings indicated that survivin and SOX9 contributed to renal tubular regeneration, whereas sustained SOX9 expression may be associated to fibrosis. CD44 was expressed in dilated tubules in the kidneys of AKI model rats and in the tubules of fibrotic areas of renal fibrosis model rats, suggesting that CD44 was expressed in renal tubules in maladaptive repair. Thus, these factors could be useful markers for detecting disruption of the regenerative mechanisms of renal tubules. We investigated immunohistochemical markers of renal tubules in adaptive and maladaptive repair in the kidneys of acute kidney injury model rats and renal fibrosis model rats. From microarray data, survivin, SOX9, and CD44 were extracted as candidate markers. Immunohistochemical analysis suggested that survivin and SOX9 contributed to renal tubular regeneration, whereas sustained SOX9 expression may be associated to fibrosis. CD44 was expressed in renal tubules in maladaptive repair. Thus, these factors could be useful markers for predicting kidney injury reversibility.
ISSN:0260-437X
1099-1263
DOI:10.1002/jat.4069