Clinical value of INSL3 in the diagnosis and development of diabetic nephropathy

Abstract

Background Insulin‐like factor 3 (INSL3) was stated to be an essential regulator in many diseases. This present study aimed to explore the underlying mechanisms of INSL3 in diabetic nephropathy (DN). Methods The serum samples were obtained from 121 DN patients, 67 T2DM patients, and 44 healthy controls. Twenty SD rats were used to establish the DN model in vivo. Quantitative PCR (qPCR) and Western blot were completed to analyze the INSL3 expression in cells, serum samples, and kidney of the rats. The structure of kidney was analyzed by HE staining. The diagnostic values of INSL3 in DN were determined by receiver operating characteristic (ROC) assay. Then, Spearman's correlation analysis was executed to verify the association between INSL3 and glomerular filtration rate (eGFR). Finally, the proliferation and apoptosis status of transfected cells were analyzed by MTT, flow cytometry, and Hoechst33258 staining assay. Results We found that INSL3 expression was up‐regulated in DN patients and SV40‐MES‐13 cells. Furthermore, the correlation analysis elucidated that INSL3 expression was negatively correlated with DN diagnosis golden criterion eGFR. INSL3 knockdown promoted the proliferation rate and inhibited the apoptosis rate of SV40‐MES‐13 cells after high‐glucose treatment. Finally, the INSL3 expression and fast blood glucose were up‐regulated in DN rats. Conclusions Collectively, this study demonstrated the clinical significance of INSL3 in diagnosing and developing DN.

Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort

“…It is also associated with the maintenance of bone strength; genetic defects for either INSL3 or its cognate receptor RXFP2 in mice and humans are linked to osteopenia and osteoporosis 11 . INSL3 has additionally been suggested to ameliorate liver fibrosis 12 as well as deteriorating kidney function 13 …”

“…11 INSL3 has additionally been suggested to ameliorate liver fibrosis 12 as well as deteriorating kidney function. 13 Following an initial cross-sectional study of community-living men in Australia, 14,15 the present investigation was aimed at developing a more detailed understanding of the relationship between circulating INSL3 and hormonal/lifestyle factors in a larger multicenter European population of community-dwelling aging men. This population study takes advantage of the extensive phenotyping carried out in the EMAS cohort and additionally profits from the longitudinal nature of this study in addition to the cross-sectional data.…”

The Leydig cell biomarker INSL3 as a predictor of age-related morbidity: Findings from the EMAS cohort

“…Firstly, and strongly supported by the present findings, INSL3 is known to promote bone metabolism, with genetic defects in the receptor RXFP2 in mice and humans both leading to osteoporosis and osteopenia ( 24 ), and with clear effects on bone cells in culture ( 25 ). Next, recent evidence suggests a role for INSL3 in the liver to reduce fibrosis ( 28 ), and in the kidney to promote healthy kidney function ( 29 ). Finally, RXFP2 receptors are known to be located within the testes, not only on germ cells, where they are believed to promote spermatogenesis, but also on the Leydig cells themselves ( 30 ).…”

Expression and Role of INSL3 in the Fetal Testis

“…INSL3 may have roles beyond fetal life, in both adult males and females. These may be relicts of ancestral functions prior to the emergence of mammals and the acquisition of new roles and include support of gametogenesis ( 8 , 22 , 23 ) and bone metabolism ( 24 ), and possibly also improvement of kidney function ( 25 ). In female mammals INSL3 is expressed by the equivalent cells in the ovary to Leydig cells, the theca interna cells of growing antral follicles.…”