TRANSFORMING GROWTH FACTOR-BETA(1) AND FORSKOLIN MODULATE GAP JUNCTIONAL COMMUNICATION AND CELLULAR PHENOTYPE OF CULTURED SCHWANN-CELLS

Following peripheral nerve injury, Schwann cells undergo a series of c ellular alterations that are thought to assist the regenerative proces s. Some of these changes are stimulated by the local release of cytoki nes and mitogenic factors. To test the hypothesis that cytokine regula tion of gap junctional communication between cells helps to coordinate Schwann cell responses, cultured rat Schwann cells, from sciatic nerv e, were utilized to study phasic changes induced by transforming growt h factor-beta(1) (TGF beta(1)), a cytokine released after nerve injury , or forskolin in combination with bovine pituitary extract (F-BPE), k nown for its mitogenic effects in vitro. In mitotically quiescent cult ures, TGF beta(1) significantly decreased both electrical and dye coup ling mediated by gap junctions. Single-channel analysis revealed that cultured Schwann cells expressed gap junctions with two distinct chann el sizes of about 26 pS and 44 pS. TGF beta(1) treatment reduced coupl ing due to both populations of channels. Exposure to TGF beta(1) had a minimal effect on proliferation but significantly altered cellular mo rphology; cell bodies became flattened with multipolar processes withi n 72 hr. Additionally, immunolabeling for both low-affinity nerve grow th factor receptor (L-NGFR) and glial fibrillary acidic protein (GFAP) were reduced, suggesting increased differentiation. In contrast, trea tment with F-BPE significantly enhanced both electrical and dye coupli ng and stimulated Schwann cell proliferation. Additionally, cell bodie s became more rounded with polarized, cytoplasmic processes contiguous ly aligned with adjacent cells. F-BPE reduced immunolabeling for L-NGF R but increased expression of both GFAP and the major peripheral myeli n protein, P-o. These data indicate that TGF beta(1) and/or F-BPE indu ce phenotypic changes in Schwann cells, including the coordinated regu lation of proliferation and modulation of intercellular communication via gap junctions. Such mechanisms may underlie phasic responses that orchestrate recovery from nerve injury, indicating that Schwann cell g ap junctions may be critical for peripheral nerve function.