Abstract P029: Variable Expression Of Integrin Subunits In The Male And Female Kidneys Suggests A Key Factor Responsible For The Higher Prevalence Of Chronic Kidney Diseases In Women

Abstract

Clinical and epidemiological studies have highlighted the sex differences in the incidence of chronic kidney diseases. However, the underlying pathological mechanisms contributing to the higher prevalence of chronic kidney disease in women are not well known. The cell’s reciprocal communication to the basement membrane is one of the important factors in maintaining kidney functions and injury responses. The cell-basement membrane communication is mediated by cell surface receptors. Integrins are heterodimeric cell surface receptors that consist of noncovalently associated α and β subunits and are the principal receptor that transduces signaling between the cell and basement membrane. This study investigated the sex difference in the expression pattern of integrin α2, α5, and integrin β1. The kidney cortex from 2 months old C57BL/6 mice (both male and female) was investigated for the expression pattern of integrin using q-RTPCR and immunoblotting. Immunoblotting shows a 35% decrease in integrin β1 protein in females (1.13±0.15) compared to males (1.73±0.36). This was further confirmed by the fold change in mRNA expression using q-RTPCR that shows significantly lower integrin β1 mRNA levels in females compared to males 1.097 ± 0.08 (male) and 0.693± 0.11(female). The expression of collagen receptor, integrin α2 did not show a significant difference in expression between males and females in immunoblotting (0.23±0.14 vs 0.78±0.35) and q-RTPCR (1.07±0.46 vs 1.36±0.47). The receptor for fibronectin, integrin α5 also did not alter between males and females by immunoblotting (1.00±0.28 vs 0.98±0.17) and q-RTPCR (1.05±0.55 vs 1.04±0.38). The cell-specific expression in kidneys is progressing using immune histochemistry and primary cell cultures. Integrin β1 KO mice developed higher fibrosis than WT mice when subjected to injury. This observed lower integrin β1 expression could be an important factor in the modification of cell microenvironment and contributes to the higher chronic kidney disease progression in women that require further investigation.