PMID- 7856721 OWN - NLM STAT- MEDLINE DCOM- 19950315 LR - 20181113 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 146 IP - 1 DP - 1995 Jan TI - Myofibroblasts in experimental hydronephrosis. PG - 121-9 AB - Interstitial fibrosis is a common outcome of longterm ureteral obstruction. One pathological arm of the fibrotic reaction in diverse tissue loci and experimental models is the retraction of granulation tissue. The role of the myofibroblast in granulation tissue contraction and fibrocontractive diseases has been well established, but the mechanisms leading to differentiation of fibroblastic cells into myofibroblasts during the evolution of inflammation are not yet fully clarified. Investigators using other model systems have shown that macrophage-derived transforming growth factor-beta 1 (TGF-beta 1) may be pivotal in the process of myofibroblast modulation. Our laboratory has shown that the unilateral ureteral obstruction in the rat is characterized by a 20-fold increment in infiltrating renal cortical interstitial macrophages, an increase in cortical TGF-beta 1 gene expression, which parallels the infiltrating macrophage burden, and immunolocalization of this peptide growth factor in close proximity to resident interstitial fibroblasts. Because of this model's features, it was our aim to assess whether a myofibroblastic modulation was operant in the renal cortex of obstructed rat kidneys versus the control contralateral unobstructed kidney specimens. Immunolabeling for alpha-smooth muscle actin and the intermediate filament protein, desmin, was detected and steadily intensified from 24 to 96 hours after unilateral ureteral obstruction in obstructed kidneys only. In temporal concert with the detection of alpha-smooth muscle actin protein, the mRNA expression for this cytoskeletal component exhibited 3.7-, 15.7-, and 4.1-fold increments in the renal cortex of obstructed kidneys versus the contralateral unobstructed kidney specimens at 24, 48, and 96 hours after unilateral ureteral obstruction, respectively. Whole body X-irradiation, administered to rats 11 days before proximal left ureteral ligation, significantly lowered cortical interstitial macrophage number, cortical TGF-beta and alpha-smooth muscle actin mRNA levels as well as the intensity of immunolabeling for alpha-smooth muscle actin from 12 to 96 hours after unilateral ureteral obstruction. These data support a postulate that renal cortical TGF-beta 1, derived from the infiltrating macrophage, in part, contributes to the subsequent interstitial fibrosis response to renal injury by fostering the modulation of fibroblasts to myofibroblasts within the renal cortex after ureteral obstruction. FAU - Diamond, J R AU - Diamond JR AD - Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033. FAU - van Goor, H AU - van Goor H FAU - Ding, G AU - Ding G FAU - Engelmyer, E AU - Engelmyer E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Actins) RN - 0 (Desmin) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Actins/analysis MH - Animals MH - Base Sequence MH - Blotting, Northern MH - Cell Differentiation/physiology MH - Desmin/analysis MH - Fibroblasts/chemistry/*pathology MH - Hydronephrosis/*pathology MH - Immunoenzyme Techniques MH - Kidney/chemistry/*pathology MH - Male MH - Molecular Sequence Data MH - Muscle, Smooth/cytology MH - RNA, Messenger/analysis MH - Rats MH - Rats, Sprague-Dawley MH - Transforming Growth Factor beta/analysis MH - Whole-Body Irradiation PMC - PMC1870756 EDAT- 1995/01/01 00:00 MHDA- 1995/01/01 00:01 PMCR- 1995/07/01 CRDT- 1995/01/01 00:00 PHST- 1995/01/01 00:00 [pubmed] PHST- 1995/01/01 00:01 [medline] PHST- 1995/01/01 00:00 [entrez] PHST- 1995/07/01 00:00 [pmc-release] PST - ppublish SO - Am J Pathol. 1995 Jan;146(1):121-9.