Differential expressions of mRNA for proteoglycans, collagens and transforming growth factor-beta in the human cervix during pregnancy and involution.
During pregnancy and involution, an extensive remodelling of the human cervical connective tissue occurs. This cervical ripening is one of the most pronounced physiological remodelling processes known in human connective tissue. To investigate how the remodelling is accomplished, the levels of mRNA for collagen I and III, versican and three small proteoglycans, biglycan, decorin and fibromodulin, were evaluated using Northern blots at different stages of cervical ripening. In the corresponding biopsies the concentration of collagen and of small and large proteoglycans were determined. The role of transforming growth factor-beta (TGF-beta) as a mediator of the remodelling process was also investigated. The concentration of collagen decreased and 1 week before partus, 50% of the nonpregnant level was attained. No further decrease was noted after partus. The mRNA for collagen I and III did, however, not decrease in the term pregnant cervix 1 week before partus. Only 20-30% decrease during the final ripening just before partus was recorded. Neither did the mRNA levels of the small proteoglycans change significantly during the ripening, despite an almost 50% decrease in the concentration of the small proteoglycans. The message for versican was, however, 5-fold increased at partus and then gradually returned to nonpregnant levels within 4 days after delivery. These changes corresponded to similar changes in the concentration of the large proteoglycan. Thus, the remodelling of the cervical connective tissue is achieved by two different mechanisms, on one hand an increased turnover of collagen and the small proteoglycans, on the other a changed transcription followed by an increased production of versican. During the involution 2- to 3-fold increases in the messages for collagen I and III, and the small proteoglycans, biglycan and decorin, corresponded to increases in the concentration of the small proteoglycans and non-extractable collagen. The message for TGF-beta was increased 2-fold immediately after delivery compared with the term pregnant state. Thus, TGF-beta may be of importance for the reconstruction of the cervix, which starts immediately after partus.
Westergren-Thorsson
G
G
Department of Physiological Chemistry, Lund University, Lund, Sweden.
Norman
M
M
Björnsson
S
S
Endrésen
U
U
Stjernholm
Y
Y
Ekman
G
G
Malmström
A
A
D000328:Adult; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002584:Cervix Uteri / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D003238:Connective Tissue / Q000378:metabolism*; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005260:Female; D000071235:Fibromodulin; D006801:Humans; D037181:Lectins, C-Type; D008875:Middle Aged; D049590:Postpartum Period / Q000378:metabolism*; D011247:Pregnancy; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D053675:Versicans
D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C508322:VCAN protein, human; D000071235:Fibromodulin; D053675:Versicans; D003094:Collagen