FXIII-A activity regulates proliferation of preadipocytes by promoting pFN assembly into preadipocyte extracellular matrix. (A) Exogenous pFN immobilized onto culture plates (white circles) or added to media (black circles) under serum-free conditions promotes preadipocyte proliferation in a concentration-dependent manner (n = 4). (B) Blocking antibody toward EDA-FN (white triangle) further increased pFN-mediated preadipocyte proliferation, suggesting that the 2 forms of FN have opposing functions. Control treatment; isotype antibody (black circles) (n = 3). **P < .01. (C) Media supplemented with pFN potentiates the proproliferative effect of INS on preadipocytes under serum-free conditions. The combined effect of pFN and INS on preadipocyte proliferation is inhibited by NC9 (n = 3). *** or ^###P < .001 (D) The proproliferative effect of INS on preadipocytes under serum-free conditions is mediated by the INS receptor (IR) and not by the INS-like growth factor receptor (IGFR), as demonstrated by the ability of respective receptor inhibitors to block the effect. Only the IR inhibitor HNMPA-(AM)3 (10 µM) reduced proliferation caused by combined pFN and INS treatment; addition of the IGFR inhibitor (PPP, 10 µM) had the opposite effect. Proproliferative effects of pFN alone were not mediated by either IR or IGFR. n = 3, *P < .05; **P < .01; N.S, not significant. Error bars represent SEM.