Transforming growth factor-β1 (TGF-β1) is sufficient to induce fibrosis of rabbit corpus cavernosum in vivo

Purpose: The pleotropic cytokine TGF-beta(1) which induces connective tissue synthesis, and inhibits the growth of smooth muscle cells, has been implicated in corpus cavernosum fibrosis. The objective of this study was to determine the dose and time dependence of TGF-beta(1) as an active agent in penile corporal fibrosis in an animal model. Materials and Methods: A time release method of delivery was developed using sodium alginate microspheres containing recombinant human (rh) TGF-beta(1). New Zealand White rabbits were injected intracorporally with a single alginate microsphere either with or without rh-TGF-beta(1). Dosage was varied from 325 to 1500 ng./bead. Animals were sacrificed at either three or five days post injection and the penises removed en bloc, examined, and processed for quantitative histomorphometric analysis, staining the sections with Masson's trichrome. Results: Alginate microspheres containing [I-125]-rh-TGF-beta(1) showed slow-release kinetics (t(1/2) = 10.5 hours). Histomorphometric analysis of 60 sets of high powered fields/treatment/animal showed dose dependent decreases in percentage of corporal smooth muscle with TGF-beta(1) treatment (750 to 1500 ng./bead). Placebo (alginate microspheres alone) had trabecular smooth muscle content comparable to values previously reported for untreated rabbit corpus cavernosum. Conclusions: This study confirms that TGF-beta(1) induces fibrosis in situ by altering connective tissue synthesis and hence the structure of the corpus cavernosum. Injection of rh-TGF-beta(1) impregnated alginate microspheres into the corpus cavernosum resulted in dose-dependent decreases in percentage of corporal smooth muscle.