Back to Search
Start Over
The Role of the EGF Receptor in Sex Differences in Kidney Injury
- Source :
- J Am Soc Nephrol
- Publication Year :
- 2018
-
Abstract
- Background Sex differences mediating predisposition to kidney injury are well known, with evidence indicating lower CKD incidence rates and slower decline in renal function in nondiabetic CKD for premenopausal women compared with men. However, signaling pathways involved have not been elucidated to date. The EGF receptor (EGFR) is widely expressed in the kidney in glomeruli and tubules, and persistent and dysregulated EGFR activation mediates progressive renal injury. Methods To investigate the sex differences in response to renal injury, we examined EGFR expression in mice, in human kidney tissue, and in cultured cell lines. Results In wild type mice, renal mRNA and protein EGFR levels were comparable in males and females at postnatal day 7 but were significantly lower in age-matched adult females than in adult males. Similar gender differences in renal EGFR expression were detected in normal adult human kidneys. In Dsk5 mutant mice with a gain-of-function allele that increases basal EGFR kinase activity, males had progressive glomerulopathy, albuminuria, loss of podocytes, and tubulointerstitial fibrosis, but female Dsk5 mice had minimal kidney injury. Oophorectomy had no effect on renal EGFR levels in female Dsk5 mice, while castration protected against the kidney injury in male Dsk5 mice, in association with a reduction in EGFR expression to levels seen in females. Conversely, testosterone increased EGFR expression and renal injury in female Dsk5 mice. Testosterone directly stimulated EGFR expression in cultured kidney cells. Conclusions These studies indicate that differential renal EGFR expression plays a role in the sex differences in susceptibility to progressive kidney injury that may be mediated at least in part by testosterone.
- Subjects :
- Male
medicine.medical_specialty
Ovariectomy
Renal function
urologic and male genital diseases
Kidney
Cell Line
Erlotinib Hydrochloride
Mice
Sex Factors
Glomerulopathy
Internal medicine
medicine
Animals
Humans
Testosterone
Castration
RNA, Messenger
Kinase activity
Renal Insufficiency, Chronic
Protein Kinase Inhibitors
Alleles
business.industry
Podocytes
Age Factors
Glomerulosclerosis
General Medicine
Middle Aged
medicine.disease
ErbB Receptors
Mice, Inbred C57BL
Endocrinology
medicine.anatomical_structure
Basic Research
Nephrology
Gain of Function Mutation
Albuminuria
Tubulointerstitial fibrosis
Female
medicine.symptom
business
Subjects
Details
- ISSN :
- 15333450
- Volume :
- 30
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Accession number :
- edsair.doi.dedup.....c0601cfd938339c74cace5cf099553bb