Identification of potential target genes associated with the reversion of androgen-dependent skeletal muscle atrophy

Priscila de O Coelho; Flavia A Guarnier; Leonardo Bruno Figueiredo; Livia S Zaramela; Enio S A Pacini; Rosely O Godinho; Marcelo D Gomes

doi:10.1016/j.abb.2019.01.009

Identification of potential target genes associated with the reversion of androgen-dependent skeletal muscle atrophy

Arch Biochem Biophys. 2019 Mar 15:663:173-182. doi: 10.1016/j.abb.2019.01.009. Epub 2019 Jan 11.

Authors

Priscila de O Coelho¹, Flavia A Guarnier², Leonardo Bruno Figueiredo³, Livia S Zaramela¹, Enio S A Pacini³, Rosely O Godinho³, Marcelo D Gomes⁴

Affiliations

¹ Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
² Laboratory of Pathophysiology and Muscle Adaptation, State University of Londrina, Londrina, Brazil.
³ Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
⁴ Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Brazil. Electronic address: mdamario@fmrp.usp.br.

PMID: 30639329
DOI: 10.1016/j.abb.2019.01.009

Abstract

Muscle wasting or atrophy is extensively associated with human systemic diseases including diabetes, cancer, and kidney failure. Accumulating evidence from transcriptional profiles has noted that a common set of genes, termed atrogenes, is modulated in atrophying muscles. However, the transcriptional changes that trigger the reversion or attenuation of muscle atrophy have not been characterized at the molecular level until now. Here, we applied cDNA microarrays to investigate the transcriptional response of androgen-sensitive Levator ani muscle (LA) during atrophy reversion. Most of the differentially expressed genes behaved as atrogenes and responded to castration-induced atrophy. However, seven genes (APLN, DUSP5, IGF1, PIK3IP1, KLHL38, PI15, and MKL1) did not respond to castration but instead responded exclusively to testosterone replacement. Considering that almost all proteins encoded by these genes are associated with the reversion of atrophy and may function as regulators of cell proliferation/growth, our results provide new perspectives on the existence of anti-atrogenes.

Keywords: And atrophy reversion; Atrogenes; FBXO32; Muscle atrophy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Androgens / metabolism*
Animals
Fasting
Gene Expression Profiling*
Hormone Replacement Therapy
Male
Mice
Models, Biological
Muscle, Skeletal / metabolism*
Muscle, Skeletal / pathology
Muscular Atrophy / metabolism*
Oligonucleotide Array Sequence Analysis
Orchiectomy
Rats
Rats, Wistar
Testosterone / administration & dosage

Substances

Androgens
Testosterone