科研之友
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Introduction. @@@ Previously we reported that paracrine actions likely mediated the therapeutic effects of adipose tissue-derived stem cells (ADSCs) on a rat model of cavernous nerve (CN) injury. @@@ Aim. @@@ To identify potential neurotrophic factors in ADSC's secretion, test the most promising one, and identify the molecular mechanism of its neurotrophic action. @@@ Methods. @@@ Rat major pelvic ganglia (MPG) were cultured in conditioned media of ADSC and penile smooth muscle cells (PSMCs). Cytokine expression in these two media was probed with a cytokine antibody array. CXCL5 cytokine was quantified in these two media by enzyme-linked immunosorbent assay (ELISA). Activation of Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) by CXCL5 was tested in neuroblastoma cell lines BE(2)C and SH-SY5Y as well as in Schwann cell line RT4-D6P2T by Western blot. Involvement of CXCL5 and JAK/STAT in ADSC-conditioned medium's neurotrophic effects was confirmed with anti-CXCL5 antibody and JAK inhibitor AG490, respectively. @@@ Main Outcome Measures. @@@ Neurotrophic effects of ADSC and PSMC-conditioned media were quantified by measuring neurite length in MPG cultures. Secretion of CXCL5 in these two media was quantified by ELISA. Activation of JAK/STAT by CXCL5 was quantified by densitometry on Western blots for STAT1 and STAT3 phosphorylation. @@@ Results. @@@ MPG neurite length was significantly longer in ADSC than in PSMC-conditioned medium. CXCL5 was secreted eight times higher in ADSC than in PSMC-conditioned medium. Anti-CXCL5 antibody blocked the neurotrophic effects of ADSC-conditioned medium. CXCL5 activated JAK/STAT concentration-dependently from 0 to 50 ng/mL in RT4-D6P2T Schwann cells. At 50 ng/mL, CXCL5 activated JAK/STAT time-dependently, peaking at 45 minutes. AG490 blocked these activities as well as the neurotrophic effects of ADSC-conditioned medium. @@@ Conclusions. @@@ CXCL5 was secreted by ADSC at a high level, promoted MPG neurite growth, and activated JAK/STAT in Schwann cells. CXCL5 may contribute to ADSC's therapeutic efficacy on CN injury-induced ED. Zhang H, Yang R, Wang Z, Lin G, Lue TF, and Lin C-S. Adipose tissue-derived stem cells secrete CXCL5 cytokine with neurotrophic effects on cavernous nerve regeneration. J Sex Med 2011;8:437-446.
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