Renovascular disease induces mitochondrial damage in swine scattered tubular cells

Arash Aghajani Nargesi, Xiang Yang Zhu, Sabena M. Conley, John R. Woollard, Ishran M. Saadiq, Lilach O. Lerman, Alfonso Eirin

Research output: Contribution to journalArticle

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Abstract

Scattered tubular-like cells (STCs) contribute to repair neighboring injured renal tubular cells. Mitochondria mediate STC biology and function but might be injured by the ambient milieu. We hypothesized that the microenviroment induced by the ischemic and metabolic components of renovascular disease impairs STC mitochondrial structure and function in swine, which can be attenuated with mitoprotection. CD24+/CD133+ STCs were quantified in pig kidneys after 16 wk of metabolic syndrome (MetS) or lean diet (Lean) with or without concurrent renal artery stenosis (RAS) (n = 6 each). Pig STCs were isolated and characterized, and mitochondrial structure, membrane potential, and oxidative stress were assessed in cells untreated or incubated with the mitoprotective drug elamipretide (1 nM for 6 h). STC-protective effects were assessed in vitro by their capacity to proliferate and improve viability of injured pig tubular epithelial cells. The percentage of STCs was higher in MetS, Lean + RAS, and MetS + RAS kidneys compared with Lean kidneys. STCs isolated from Lean + RAS and MetS + RAS pigs showed mitochondrial swelling and decreased matrix density, which were both restored by mitoprotection. In addition, mitochondrial membrane potential and ATP production were reduced and production of reactive oxygen species elevated in MetS, Lean + RAS, and MetS + RAS STCs. Importantly, mitoprotection improved mitochondrial structure and function as well as the capacity of MetS + RAS STCs to repair injured tubular cells in vitro. Renovascular disease in swine is associated with a higher prevalence of STCs but induces structural and functional alterations in STC mitochondria, which impair their reparative potency. These observations suggest a key role for mitochondria in the renal reparative capacity of STCs.

Original languageEnglish (US)
Pages (from-to)F1142-F1153
JournalAmerican journal of physiology. Renal physiology
Volume317
Issue number5
DOIs
StatePublished - Nov 1 2019

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Mitochondrial Diseases
Swine
Renal Artery Obstruction
Kidney
Mitochondria
Mitochondrial Membrane Potential
Swine Diseases
Mitochondrial Swelling

Keywords

  • metabolic syndrome
  • mitochondria
  • renal artery stenosis
  • renovascular disease
  • scattered tubular cells

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Renovascular disease induces mitochondrial damage in swine scattered tubular cells. / Nargesi, Arash Aghajani; Zhu, Xiang Yang; Conley, Sabena M.; Woollard, John R.; Saadiq, Ishran M.; Lerman, Lilach O.; Eirin, Alfonso.

In: American journal of physiology. Renal physiology, Vol. 317, No. 5, 01.11.2019, p. F1142-F1153.

Research output: Contribution to journalArticle

Nargesi, Arash Aghajani ; Zhu, Xiang Yang ; Conley, Sabena M. ; Woollard, John R. ; Saadiq, Ishran M. ; Lerman, Lilach O. ; Eirin, Alfonso. / Renovascular disease induces mitochondrial damage in swine scattered tubular cells. In: American journal of physiology. Renal physiology. 2019 ; Vol. 317, No. 5. pp. F1142-F1153.
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AU - Zhu, Xiang Yang

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AU - Saadiq, Ishran M.

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