Epidermal growth factor attenuates tubular necrosis following mercuric chloride damage by regeneration of indigenous, not bone marrow‐derived cells. Issue 2 (11th November 2014)

• Record Type: Journal Article
• Authors: Yen, Tzung‐Hai; Alison, Malcolm R.; Goodlad, Robert A.; Otto, William R.; Jeffery, Rosemary; Cook, H. Terence; Wright, Nicholas A.; Poulsom, Richard
• Is Part Of: Journal of cellular and molecular medicine. Volume 19:Issue 2(2015)
• Page Start: 463
• Page End: 473
• Publication Date: 2014-11-11
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12478
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12478-abs-0001"> <title>Abstract</title> <p>To assess effects of epidermal growth factor (EGF) and pegylated granulocyte colony‐stimulating factor (P‐GCSF; pegfilgrastim) administration on the cellular origin of renal tubular epithelium regenerating after acute kidney injury initiated by mercuric chloride (HgCl<sub>2</sub>). Female mice were irradiated and male whole bone marrow (BM) was transplanted into them. Six weeks later recipient mice were assigned to one of eight groups: control, P‐GCSF+, EGF+, P‐GCSF+EGF+, HgCl<sub>2</sub>, HgCl<sub>2</sub>+P‐GCSF+, HgCl<sub>2</sub>+EGF+ and HgCl<sub>2</sub>+P‐GCSF+EGF+. Following HgCl<sub>2</sub>, injection tubular injury scores increased and serum urea nitrogen levels reached uraemia after 3 days, but EGF‐treated groups were resistant to this acute kidney injury. A four‐in‐one analytical technique for identification of cellular origin, tubular phenotype, basement membrane and S‐phase status revealed that BM contributed 1% of proximal tubular epithelium in undamaged kidneys and 3% after HgCl<sub>2</sub> damage, with no effects of exogenous EGF or P‐GCSF. Only 0.5% proximal tubular cells were seen in S‐phase in the undamaged group kidneys; this increased to 7–8% after HgCl<sub>2</sub> damage and to 15% after addition of EGF. Most of the regenerating tubular epithelium originated from the indigenous pool. BM contributed up to 6.6% of the proximal tubular cells in S‐phase after HgCl<sub>2</sub> damage, but only to 3.3% after additional EGF. EGF administration attenuated tubular necrosis following HgCl<sub>2</sub> damage, and the major cause of this protective effect was division of indigenous cells, whereas BM‐derived cells were less responsive. P‐GCSF did not influence damage or regeneration.</p> </abstract>