RGD Reference Report - Control of the epidermal growth factor receptor and its ligands during renal injury. - Rat Genome Database

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Control of the epidermal growth factor receptor and its ligands during renal injury.

Authors: Hise, MK  Salmanullah, M  Liu, L  Drachenberg, CI  Papadimitriou, JC  Rohan, RM 
Citation: Hise MK, etal., Nephron. 2001 May;88(1):71-9.
RGD ID: 10395241
Pubmed: PMID:11340354   (View Abstract at PubMed)
DOI: DOI:45962   (Journal Full-text)

AIM: We studied control of the epidermal growth factor (EGF) receptor and its ligands during kidney injury, since they may be importantly involved in repair. METHODS: The folic acid model of renal injury was used in these studies. Messenger RNA (mRNA) was evaluated by solution hybridization. Immunohistochemistry of transforming growth factor alpha (TGF-alpha) was also performed. RESULTS: Twenty-four hours after folic acid induced acute renal injury, creatinine increased from 0.3 +/- 0.03 mg/dl in controls to 2.0 +/- 0.8 mg/dl in folic acid injured kidneys (n = 4, p < 0.03). mRNA for the EGF receptor was increased nearly sevenfold by 24 h, and mRNA for the receptor was increased as early as 1 h following folic acid treatment. EGF receptor ligand caused a profound downregulation of the receptors in proximal tubule basolateral membranes, but receptors returned rapidly to the membrane surface in injured kidneys. The mRNA levels for heparin-binding EGF and TGF-alpha, two EGF receptor ligands, increased within 1 h of injury. TGF-alpha mRNA increased from 1.0 +/- 0.09 (relative densitometry units) in control animals to 2.9 +/- 0.13 in folic acid treated rats at 24 h (n = 4, p < 0.01), and immunohistochemical staining for TGF-alpha increased in injured kidneys at distal nephron sites. CONCLUSIONS: These studies indicate that upregulation of the EGF receptor is related to an increase in mRNA. The rapid return of receptors to the membrane surface following ligand stimulation may be useful in maintaining a mitogenic stimulus. Multiple EGF-like ligands may be important in activating the upregulated EGF receptor during repair from renal injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acute kidney failure  ISOEgf (Rattus norvegicus)10395241; 10395241mRNA:decreased expression:kidneyRGD 
acute kidney failure  ISOEgfr (Rattus norvegicus)10395241; 10395241mRNA:increased expression:kidneyRGD 
acute kidney failure  IEP 10395241mRNA:decreased expression:kidneyRGD 
acute kidney failure  IEP 10395241; 10395241; 10395241mRNA:increased expression:kidneyRGD 
acute kidney failure  ISOHbegf (Rattus norvegicus)10395241; 10395241mRNA:increased expression:kidneyRGD 
acute kidney failure  ISOTgfa (Rattus norvegicus)10395241; 10395241mRNA:increased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Egf  (epidermal growth factor)
Egfr  (epidermal growth factor receptor)
Hbegf  (heparin-binding EGF-like growth factor)
Tgfa  (transforming growth factor alpha)

Genes (Mus musculus)
Egf  (epidermal growth factor)
Egfr  (epidermal growth factor receptor)
Hbegf  (heparin-binding EGF-like growth factor)
Tgfa  (transforming growth factor alpha)

Genes (Homo sapiens)
EGF  (epidermal growth factor)
EGFR  (epidermal growth factor receptor)
HBEGF  (heparin binding EGF like growth factor)
TGFA  (transforming growth factor alpha)


Additional Information