EARLY MOLECULAR RESPONSE TO RABBIT BLADDER OUTLET OBSTRUCTION

Partial obstruction of the rabbit bladder outlet induces a rapid hypertrophy characterized by increased bladder weight and smooth muscle content in addition to increased collagen deposition. In experiments designed to examine the genetic basis of this response, we evaluated the expression of a multitude of gene products in the rabbit bladder during the first 48-hr period following placement of a urethral cuff blocking the rabbit bladder outlet by 90%. Individual bladders were obtained from unoperated rabbits, from sham-operated rabbits and from rabbits at 2, 6, 10, 24, and 48 hr after obstruction. Poly (A)+ mRNA was extracted from each of these tissues and Northern blots made from the RNAs were hybridized repeatedly with a series of probes. Corrected densitometry was utilized to assign a value to each transcript and to follow the change in expression of a given gene product over time. Although several of the gene products we analyzed for were undetectable or unchanged over this brief period, we were able to detect a substantial sustained increase in the 4.5 kb mRNA encoding basic fibroblast growth factor (bFGF) initiated by 2 hr after obstruction. Later, at 6-24 hr, we measured transient induction of transcripts encoding c-myc, heat shock 70K (hsp-70), Ha-, and N-ras. In contrast, the constitutively-expressed 2.4 kb transcript for transforming growth factor-beta (TGF-beta) transiently declined to 50% of control levels at 24 hr following obstruction. In summary, our results provide a picture of tissue in transition, with synthesis of certain growth-stimulating and stress-response products (bFGF, myc, ras, and hsp-70) increasing and a growth-inhibitory substance (TGF-beta) decreasing.