Expression of platelet-derived growth factor (PDGF) in the epididymis and analysis of the epididymal development in PDGF-A, PDGF-B, and PDGF receptor β deficient mice

被引:23
作者
Basciani, S
Mariani, S
Arizzi, M
Brama, M
Ricci, A
Betsholtz, C
Bondjers, C
Ricci, G
Catizone, A
Galdieri, M
Spera, G
Gnessi, L
机构
[1] Univ Roma La Sapienza, Dipartimento Fisiopatol Med, Policlin Umberto I, I-00161 Rome, Italy
[2] Univ Gothenburg, Dept Biochem Med, SE-40530 Gothenburg, Sweden
[3] Univ Naples 2, Histol & Embryol Lab, Dept Expt Med, I-80183 Naples, Italy
[4] Univ Roma La Sapienza, Dept Histol & Med Embryol, I-00161 Rome, Italy
关键词
developmental biology; epididymis; growth factors; kinases; male reproductive tract;
D O I
10.1095/biolreprod.103.019232
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The platelet-derived growth factor (PDGF) family of ligands and receptors play a pivotal role in the development of various organs. The critical importance of the PDGF-mediated signaling during embryonic development and adult physiology of the kidney and the common mesonephric origin of the epididymis and kidney prompted us to investigate the immunohistochemical localization of PDGF A- and B-chain and PDGF receptor (PDGFR) alpha- and beta-subunit in rat and mouse epididymis, the expression profiles of the corresponding mRNAs, and the consequences of a loss-of-function mutation at the PDGF-A, PDGF-B, and PDGFR-beta loci on mouse epididymis phenotypic appearance. Prenatally, PDGF-A and PDGFR-alpha immunohistochemical staining was seen in both species, whereas PDGF-B and PDGFR-beta were absent. The cellular localization of PDGF-A within the epithelium and the alpha-receptor in the mesenchyme in either mouse or rat before birth suggests that the PDGF-A/PDGFR-alpha system might be involved in the epididymal epithelial-mesenchymal interaction during the fetal period of life. Postnatally, PDGF A- and B-ligand and PDGFR alpha- and beta-subunit were confined in the epithelium. The identity of PDGF and PDGFR proteins were further confirmed by immunoblotting. In line with the immunohistochemical studies, PDGF-A and PDGFR-alpha mRNAs were seen by reverse transcription-polymerase chain reaction in rat and mouse tissue before birth, whereas PDGF-B and PDGFR-beta were almost not detectable. During the first days of life, PDGF-B and PDGFR-beta genes started to appear, and the overall trend in mRNA expression throughout postnatal development showed that the transcripts levels for PDGF-A, PDGF-B, PDGFR-beta, and PDGFR-alpha were constant with the only exception of a progressive decrease of PDGFR-alpha in adult rats. The PDGF-A null mutation strongly influenced the epididymal phenotype starting from puberty; only fetal PDGF-B and PDGFR-beta -/- mice were available, and no differences were seen in the epididymis of these animals, compared with wild-type littermates. Taken together, these data indicate that the PDGF system is highly expressed in the epididymis and suggest that PDGF could be involved in the maintenance of morphological structure and functional control of this organ.
引用
收藏
页码:168 / 177
页数:10
相关论文
共 46 条
[1]   Expression analysis of PDGF-C in adult and developing mouse tissues [J].
Aase, K ;
Abramsson, A ;
Karlsson, L ;
Betsholtz, C ;
Eriksson, U .
MECHANISMS OF DEVELOPMENT, 2002, 110 (1-2) :187-191
[2]   DEVELOPMENTAL PATTERNS OF PDGF B-CHAIN, PDGF-RECEPTOR, AND ALPHA-ACTIN EXPRESSION IN HUMAN GLOMERULOGENESIS [J].
ALPERS, CE ;
SEIFERT, RA ;
HUDKINS, KL ;
JOHNSON, RJ ;
BOWENPOPE, DF .
KIDNEY INTERNATIONAL, 1992, 42 (02) :390-399
[3]   PLATELET-DERIVED GROWTH-FACTOR A-CHAIN EXPRESSION IN DEVELOPING AND MATURE HUMAN KIDNEYS AND IN WILMS-TUMOR [J].
ALPERS, CE ;
HUDKINS, KL ;
FERGUSON, M ;
JOHNSON, RJ ;
RUTLEDGE, JC .
KIDNEY INTERNATIONAL, 1995, 48 (01) :146-154
[4]   PDGF-D is a specific, protease-activated ligand for the PDGF β-receptor [J].
Bergsten, E ;
Uutela, M ;
Li, XR ;
Pietras, K ;
Östman, A ;
Heldin, CH ;
Alitalo, K ;
Eriksson, U .
NATURE CELL BIOLOGY, 2001, 3 (05) :512-516
[5]   Angiotensin II signal transduction in vascular smooth muscle - Role of tyrosine kinases [J].
Berk, BC ;
Corson, MA .
CIRCULATION RESEARCH, 1997, 80 (05) :607-616
[6]   Developmental roles of platelet-derived growth factors [J].
Betsholtz, C ;
Karlsson, L ;
Lindahl, P .
BIOESSAYS, 2001, 23 (06) :494-507
[7]   PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis [J].
Bostrom, H ;
Willetts, K ;
Pekny, M ;
Leveen, P ;
Lindahl, P ;
Hedstrand, H ;
Pekna, M ;
Hellstrom, M ;
GebreMedhin, S ;
Schalling, M ;
Nilsson, M ;
Kurland, S ;
Tornell, J ;
Heath, JK ;
Betsholtz, C .
CELL, 1996, 85 (06) :863-873
[8]   Pdgfr-α mediates testis cord organization and fetal Leydig cell development in the XY gonad [J].
Brennan, J ;
Tilmann, C ;
Capel, B .
GENES & DEVELOPMENT, 2003, 17 (06) :800-810
[9]  
BURTON PBJ, 1993, INT J EXP PATHOL, V74, P87
[10]  
Fruttiger M, 1999, DEVELOPMENT, V126, P457