TY - JOUR
T1 - Renal cell regeneration following oxidant exposure
T2 - Inhibition by TGF-β1, and stimulation by ascorbic acid
AU - Nowak, Grazyna
AU - Schnellmann, Rick G.
N1 - Funding Information:
This work was supported by a grant from National Institute of Environmental Health Sciences, NIH (ES-04110). We thank Dr. Kevin Phelan for the use of his microscope, Jonathan Ishmael and Douglas McKeller for their excellent technical assistance, and Wendy Waegell (Celtrix Pharmaceuticals, Inc.) for the generous gift of the monoclonal anti-TGF-β1 antibody. Portions of this work were presented at The 35th Annual Meeting of the Society of Toxicology, March 10–14, 1996, Anaheim, California, Abstract 1238.
PY - 1997/7
Y1 - 1997/7
N2 - Renal proximal tubular cell (RPTC) monolayers exposed to the model oxidant tert-butylhydroperoxide (TBHP; 0.8 mM) for 1.5 hrs were 33 and 31% confluent after 1 and 4 days, respectively. Control monolayers remained 100 confluent throughout the experiment. Exogenous TGF-β1 promoted monolayer deterioration by potentiating cellular death and suppressed EGF-stimulated regeneration of the RPTC monolayer. Net TGF-β1 production in injured RPTC increased 1.7- and 3.2-fold on Days 1 and 2, respectively, and returned to control levels 4 days following TBHP treatment. An anti-TGF-β1 antibody increased monolayer confluence to 50% and DNA content 1.3-fold 4 days after TBHP exposure. L-Ascorbic acid 2-phosphate (AscP) present only during the recovery period increased monolayer confluence to 67% but had no effect on RPTC proliferation, suggesting that AscP promoted monolayer regeneration by cellular migration/spreading. AscP present continuously had no effect on the extent of TBHP-induced injury but promoted regeneration of RPTC with increased monolayer confluence (1.8-fold) and DNA content (1.8-fold) and decreased cellular lysis by 52% 4 days following TBHP exposure. The results demonstrate that TBHP-induced injury increases net TGF-β1 production in RPTC and that autocrine TGF-β1 inhibits regeneration of the monolayer by potentiating cellular injury and monolayer deterioration. The data also show that AscP is not cytoprotective during TBHP exposure but promotes RPTC regeneration by stimulating proliferation and migration/spreading and decreasing cellular death during the recovery period.
AB - Renal proximal tubular cell (RPTC) monolayers exposed to the model oxidant tert-butylhydroperoxide (TBHP; 0.8 mM) for 1.5 hrs were 33 and 31% confluent after 1 and 4 days, respectively. Control monolayers remained 100 confluent throughout the experiment. Exogenous TGF-β1 promoted monolayer deterioration by potentiating cellular death and suppressed EGF-stimulated regeneration of the RPTC monolayer. Net TGF-β1 production in injured RPTC increased 1.7- and 3.2-fold on Days 1 and 2, respectively, and returned to control levels 4 days following TBHP treatment. An anti-TGF-β1 antibody increased monolayer confluence to 50% and DNA content 1.3-fold 4 days after TBHP exposure. L-Ascorbic acid 2-phosphate (AscP) present only during the recovery period increased monolayer confluence to 67% but had no effect on RPTC proliferation, suggesting that AscP promoted monolayer regeneration by cellular migration/spreading. AscP present continuously had no effect on the extent of TBHP-induced injury but promoted regeneration of RPTC with increased monolayer confluence (1.8-fold) and DNA content (1.8-fold) and decreased cellular lysis by 52% 4 days following TBHP exposure. The results demonstrate that TBHP-induced injury increases net TGF-β1 production in RPTC and that autocrine TGF-β1 inhibits regeneration of the monolayer by potentiating cellular injury and monolayer deterioration. The data also show that AscP is not cytoprotective during TBHP exposure but promotes RPTC regeneration by stimulating proliferation and migration/spreading and decreasing cellular death during the recovery period.
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U2 - 10.1006/taap.1997.8166
DO - 10.1006/taap.1997.8166
M3 - Article
C2 - 9221835
AN - SCOPUS:0031193937
VL - 145
SP - 175
EP - 183
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 1
ER -