Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model

Satoshi Tanimura, Katsuyuki Tanabe, Hiromasa Miyake, Kana Masuda, Keigo Tsushida, Tomoyo Morioka, Hitoshi Sugiyama, Yasufumi Sato, Jun Wada

Research output: Contribution to journalArticle

Abstract

Acute kidney injury (AKI) is frequently encountered in clinical practice, particularly secondarily to cardiovascular surgery and administration of nephrotoxic agents, and is increasingly recognized for initiating a transition to chronic kidney disease. Clarifying the pathogenesis of AKI could facilitate the development of novel preventive strategies, because the occurrence of hospital-acquired AKI is often anticipated. Vasohibin-1 (VASH1) was initially identified as an antiangiogenic factor derived from endothelial cells. VASH1 expression in endothelial cells has subsequently been reported to enhance cellular stress tolerance. Considering the importance of maintaining peritubular capillaries in preventing the progression of AKI, the present study aimed to examine whether VASH1 deletion is involved in the pathogenesis of cisplatin-induced AKI. For this, we injected male C57BL/6J wild-type (WT) and VASH1 heterozygous knockout (VASH1-/-) mice intraperitoneally with either 20 mg/kg cisplatin or vehicle solution. Seventy-two hours after cisplatin injection, increased serum creatinine concentrations and renal tubular injury accompanied by apoptosis and oxidative stress were more prominent in VASH1-/- mice than in WT mice. Cisplatin-induced peritubular capillary loss was also accelerated by VASH1 deficiency. Moreover, the increased expression of ICAM-1 in the peritubular capillaries of cisplatin-treated VASH1-/- mice was associated with a more marked infiltration of macrophages into the kidney. Taken together, VASH1 expression could have protective effects on cisplatin-induced AKI probably by maintaining the number and function of peritubular capillaries.

Original languageEnglish
Pages (from-to)F264-F274
JournalAmerican Journal of Physiology - Renal Physiology
Volume317
Issue number2
DOIs
Publication statusPublished - Aug 1 2019

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Acute Kidney Injury
Cisplatin
Kidney
Wounds and Injuries
Endothelial Cells
Intercellular Adhesion Molecule-1
Chronic Renal Insufficiency
Creatinine
Oxidative Stress
Macrophages
Apoptosis
Injections
Serum

Keywords

  • Acute kidney injury
  • Cisplatin
  • Endothelial cells
  • Peritubular capillary
  • Vasohibin-1

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model. / Tanimura, Satoshi; Tanabe, Katsuyuki; Miyake, Hiromasa; Masuda, Kana; Tsushida, Keigo; Morioka, Tomoyo; Sugiyama, Hitoshi; Sato, Yasufumi; Wada, Jun.

In: American Journal of Physiology - Renal Physiology, Vol. 317, No. 2, 01.08.2019, p. F264-F274.

Research output: Contribution to journalArticle

Tanimura, Satoshi ; Tanabe, Katsuyuki ; Miyake, Hiromasa ; Masuda, Kana ; Tsushida, Keigo ; Morioka, Tomoyo ; Sugiyama, Hitoshi ; Sato, Yasufumi ; Wada, Jun. / Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model. In: American Journal of Physiology - Renal Physiology. 2019 ; Vol. 317, No. 2. pp. F264-F274.
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