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Growth state‐regulated expression of p52(PAI‐1) in normal rat kidney cells
Author(s) -
Ryan Michael P.,
Higgins Paul J.
Publication year - 1993
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041550219
Subject(s) - vinculin , biology , focal adhesion , plasminogen activator inhibitor 1 , plasminogen activator , medicine , population , stimulation , microbiology and biotechnology , endocrinology , signal transduction , environmental health
In normal rat kidney (NRK) cells, synthesis of the 52‐kDa substrate‐associated type 1 inhibitor of plasminogen activator [p52(PAI‐1)] is linked to alterations in cell shape and substrate adhesion. Subconfluent NRK cells accumulated significantly more ventral undersurface‐associated p52(PAI‐1) compared to newly confluent or 1 ‐ to 2‐day postconfluent cultures, suggesting that p52(PAI‐1) expression was also growth state‐modulated. Since cytoarchitectural constraints function in cell growth control, changes in p52(PAI‐1) synthesis were assessed with respect to defined morphologic events that accompany growth activation of cultured NRK cells. Stimulation of low population density, quiescent NRK cells with 20% serum‐containing medium resulted in a rapid increase in matrix p52(PAI‐1) protein content (6‐ and 26‐fold after 1 and 5 hr, respectively). Growth activation in response to serum reflected elevations in p52(PAI‐1) cytoplasmic mRNA abundance, which peaked at 2 hr (125‐fold increase) and subsequently declined (100‐fold increase) at 5 hr poststimulation. Morphologic analysis indicated that quiescent NRK cells were devoid of transcytoplasmic actin filaments and focal contact‐associated vinculin. A marked increase in the fraction of cells that eleborated transcytoplasmic microfilaments and vinculin‐containing focal adhesions was evident within 5 min of serum addition. Such cytoarchitectural restructuring preceded p52(PAI‐1) induction. Morphologic reorganization and p52(PAI‐1) induction occurred prior to progression of cells through the S‐phase, indicating they are early events associated with serum stimulation in the NRK cell system. The relevance of p52(PAI‐1) induction during this growth state transition is not clear but may influence the established cytoarchitectural changes observed prior to p52(PAI‐1) induction by regulating pericellular proteolysis and, thereby, cell‐to‐substrate adhesion. © 1993 Wiley‐Liss, Inc.