Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure

Chao Wen Cheng, Abdalla Rifai, K. A. Shuk-Man, Hao A I Shui, Yuh Feng Lin, Wei Hwa Lee, Ann Chen

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background. Rise in cellular calcium is associated with acute tubular necrosis, the most common cause of acute renal failure (ARF). The mechanisms that calcium signaling induce in the quiescent tubular cells to proliferate and differentiate during acute tubular necrosis have not been elucidated. Methods. Acute tubular necrosis induced in mice by single intravenous injection of uranyl nitrate and examined after 1, 3, 7, and 14 days. Renal function was monitored and kidneys were evaluated by histology, immunohistochemistry, Western blotting, in situ hybridization, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Models of folk acid induced-ARF and ischemic/reperfusion (I/R) injury were similarly investigated. Results. Analysis of mRNA expression of intracellular calcium and phospholipid-binding proteins demonstrated selective expression of S100A6 and Annexin A2 (Anxa2) in the renal cortex with marked elevation on day 3, and gradually decline on day 7 and further attenuation on day 14. Similarly, the expression of both proteins, as demonstrated by immunohistochemistry and Western blot analysis, was increased and reached the peak level on day 7 and then gradually declined by day 14. Vimentin, a marker of dedifferentiated cells, was highly expressed during the recovery phase. Combined in situ hybridization immunohistochemistry revealed colocalization of both S100A6 and Anxa2 with proliferating cell nuclear antigen (PCNA). The universality of this phenomenon was confirmed in two other mouse acute tubular necrosis models, the ischemic-reperfusion injury and folic acid-induced ARF. Conclusion. Collectively, these findings demonstrate that S100A6 and Anxa2 expression, initiated in response to tubular injury, persist in parallel throughout the recovery process of tubular cells in acute renal failure.

Original languageEnglish
Pages (from-to)2694-2703
Number of pages10
JournalKidney International
Volume68
Issue number6
DOIs
Publication statusPublished - Dec 2005
Externally publishedYes

Fingerprint

Annexins
Calcium-Binding Proteins
Acute Kidney Injury
Necrosis
Annexin A2
Immunohistochemistry
Wounds and Injuries
Reperfusion Injury
Kidney
In Situ Hybridization
Uranyl Nitrate
Western Blotting
Calcium Signaling
Proliferating Cell Nuclear Antigen
Vimentin
Folic Acid
Intravenous Injections
Reverse Transcription
Phospholipids
Histology

Keywords

  • Acute tubular necrosis
  • Annexin A2
  • Calcium-binding proteins
  • S100A6

ASJC Scopus subject areas

  • Nephrology

Cite this

Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure. / Cheng, Chao Wen; Rifai, Abdalla; Shuk-Man, K. A.; Shui, Hao A I; Lin, Yuh Feng; Lee, Wei Hwa; Chen, Ann.

In: Kidney International, Vol. 68, No. 6, 12.2005, p. 2694-2703.

Research output: Contribution to journalArticle

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abstract = "Background. Rise in cellular calcium is associated with acute tubular necrosis, the most common cause of acute renal failure (ARF). The mechanisms that calcium signaling induce in the quiescent tubular cells to proliferate and differentiate during acute tubular necrosis have not been elucidated. Methods. Acute tubular necrosis induced in mice by single intravenous injection of uranyl nitrate and examined after 1, 3, 7, and 14 days. Renal function was monitored and kidneys were evaluated by histology, immunohistochemistry, Western blotting, in situ hybridization, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Models of folk acid induced-ARF and ischemic/reperfusion (I/R) injury were similarly investigated. Results. Analysis of mRNA expression of intracellular calcium and phospholipid-binding proteins demonstrated selective expression of S100A6 and Annexin A2 (Anxa2) in the renal cortex with marked elevation on day 3, and gradually decline on day 7 and further attenuation on day 14. Similarly, the expression of both proteins, as demonstrated by immunohistochemistry and Western blot analysis, was increased and reached the peak level on day 7 and then gradually declined by day 14. Vimentin, a marker of dedifferentiated cells, was highly expressed during the recovery phase. Combined in situ hybridization immunohistochemistry revealed colocalization of both S100A6 and Anxa2 with proliferating cell nuclear antigen (PCNA). The universality of this phenomenon was confirmed in two other mouse acute tubular necrosis models, the ischemic-reperfusion injury and folic acid-induced ARF. Conclusion. Collectively, these findings demonstrate that S100A6 and Anxa2 expression, initiated in response to tubular injury, persist in parallel throughout the recovery process of tubular cells in acute renal failure.",
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AU - Rifai, Abdalla

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AU - Lin, Yuh Feng

AU - Lee, Wei Hwa

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N2 - Background. Rise in cellular calcium is associated with acute tubular necrosis, the most common cause of acute renal failure (ARF). The mechanisms that calcium signaling induce in the quiescent tubular cells to proliferate and differentiate during acute tubular necrosis have not been elucidated. Methods. Acute tubular necrosis induced in mice by single intravenous injection of uranyl nitrate and examined after 1, 3, 7, and 14 days. Renal function was monitored and kidneys were evaluated by histology, immunohistochemistry, Western blotting, in situ hybridization, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Models of folk acid induced-ARF and ischemic/reperfusion (I/R) injury were similarly investigated. Results. Analysis of mRNA expression of intracellular calcium and phospholipid-binding proteins demonstrated selective expression of S100A6 and Annexin A2 (Anxa2) in the renal cortex with marked elevation on day 3, and gradually decline on day 7 and further attenuation on day 14. Similarly, the expression of both proteins, as demonstrated by immunohistochemistry and Western blot analysis, was increased and reached the peak level on day 7 and then gradually declined by day 14. Vimentin, a marker of dedifferentiated cells, was highly expressed during the recovery phase. Combined in situ hybridization immunohistochemistry revealed colocalization of both S100A6 and Anxa2 with proliferating cell nuclear antigen (PCNA). The universality of this phenomenon was confirmed in two other mouse acute tubular necrosis models, the ischemic-reperfusion injury and folic acid-induced ARF. Conclusion. Collectively, these findings demonstrate that S100A6 and Anxa2 expression, initiated in response to tubular injury, persist in parallel throughout the recovery process of tubular cells in acute renal failure.

AB - Background. Rise in cellular calcium is associated with acute tubular necrosis, the most common cause of acute renal failure (ARF). The mechanisms that calcium signaling induce in the quiescent tubular cells to proliferate and differentiate during acute tubular necrosis have not been elucidated. Methods. Acute tubular necrosis induced in mice by single intravenous injection of uranyl nitrate and examined after 1, 3, 7, and 14 days. Renal function was monitored and kidneys were evaluated by histology, immunohistochemistry, Western blotting, in situ hybridization, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Models of folk acid induced-ARF and ischemic/reperfusion (I/R) injury were similarly investigated. Results. Analysis of mRNA expression of intracellular calcium and phospholipid-binding proteins demonstrated selective expression of S100A6 and Annexin A2 (Anxa2) in the renal cortex with marked elevation on day 3, and gradually decline on day 7 and further attenuation on day 14. Similarly, the expression of both proteins, as demonstrated by immunohistochemistry and Western blot analysis, was increased and reached the peak level on day 7 and then gradually declined by day 14. Vimentin, a marker of dedifferentiated cells, was highly expressed during the recovery phase. Combined in situ hybridization immunohistochemistry revealed colocalization of both S100A6 and Anxa2 with proliferating cell nuclear antigen (PCNA). The universality of this phenomenon was confirmed in two other mouse acute tubular necrosis models, the ischemic-reperfusion injury and folic acid-induced ARF. Conclusion. Collectively, these findings demonstrate that S100A6 and Anxa2 expression, initiated in response to tubular injury, persist in parallel throughout the recovery process of tubular cells in acute renal failure.

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