The appearance of fibrosis in aging organs is emblematic of growing old (1). It is particularly devastating, however, when this fibrosis unexpectedly appears at an earlier stage of life as a sequelae ofinflammation, ischemia, genetic, or metabolic disease (2-4). We have been interested in this problem in kidneys. As renal fibrosis consumes tubules and the interstitium, kidney function deteriorates and the organ eventually contracts with nephron atrophy and acellular scars (5). Since interstitial fibrosis is the structural correlate of end-stage kidney disease (2), we have focused on the origin and contribution of fibroblasts.

Fibroblasts in culture have a large, elliptical nucleus with one or more nucleoli, a prominent rough endoplasmic reticulum and golgi apparatus as well as abundant mitochondria, and cytoskeleton con-taining random F-actin stress fibers and vimentin filaments. They have no formal basal lamina (6, 7), but rather disperse among the 3-dimensional fibrils of interstitial matrix (8). Fibroblasts in kidney tissue have little in the way ofdistinguishing anatomic features, and the proteins they express are not highly specific for the cell (9). Vimen-tin is not cell-specific (10) and type I collagen synthesis is generally only detectable in selected subpopulations of fibroblasts (11-14). Subpopulations of fibroblasts activated during fibrogenesis demonstrate structural features of smooth muscle cells (15), and can express a-smooth muscle actin (aSMA)(16-19), a marker of activated fibro-blasts (myofibroblasts)(20, 21). aSMA, however, is not expressed in all fibroblasts (10), suggesting that aSSMA either does not define the universe of fibroblasts or perhaps co-identifies smooth muscle cells separated from local blood vessels in injured tissue (10, 22). This acti-vation marker also does not identify resting fibroblasts, nor distin-