Novel alternative splice variant of IGF-1R and its mRNA expression patterns in BaMa and Landrace pigs

The transcript variants of Insulin-like growth factor 1 receptor (IGF-1R) and their expression profiles had never been illuminated in pigs until now. Herein, we identified IGF-1R AS02 as a novel splice variant of IGF-1R gene by RT-PCR and analyzed its mRNA expression level by qRT-PCR in liver, cartilage and muscle tissues, while also detecting the single-nucleotide polymorphism (SNP) site near the splice site of the IGF-1R gene (in intron 19) of BaMa and Landrace pigs. Results demonstrated that the IGF-1R AS02 variant showed a significantly (P less than 0.05) higher expression level in cartilage than in muscle and liver across two pig breeds respectively. The expression level of the normal transcript (IGF-1R ISO01) of IGF-1R in cartilage was markedly lower than that in the other two tissues (P less than 0.05). In cartilage, IGF-1R ISO01 expression was higher in BaMa than in Landrace (P less than 0.05), while the expression level of IGF-1R AS02 was lower in BaMa than in Landrace (P less than 0.05). The SNP was detected in intron 19 of the IGF-1R gene of BaMa and Landrace pigs. These results contributed to facilitating a better understanding of IGF-1R gene in pigs.

Functional effects of blocking VEGF/VEGFR2 signaling in the rat urinary bladder in acute and chronic CYP-induced cystitis

High expression of VEGF is associated with immature angiogenesis within the urinary bladder wall and bladder afferent nerve sensitization, leading to visceral hyperalgesia and pelvic pain. Research suggests a shift in VEGF alternative splice variant (VEGF-Axxxa and VEGF-Axxxb) expression with several pathologies (e.g., neuropathic pain and inflammation) as well as differing effects on pain. Translational studies have also demonstrated increased total VEGF expression in the bladders of women with interstitial cystitis/bladder pain syndrome. In the present study, we quantified VEGF alternative splice variant expression in lower urinary tract tissues under control conditions and with cyclophosphamide (CYP)-induced cystitis. Using conscious cystometry and intravesical instillation of a potent and selective VEGF receptor 2 (VEGFR2) tyrosine kinase inhibitor (Ki-8751, 1 mg/kg) in Wistar rats (male and female) with acute and chronic CYP-induced cystitis and control (no CYP) rats, we further determined the functional effects of VEGFR2 blockade on bladder function. With VEGFR2 blockade, bladder capacity increased ( P ≤ 0.01) in male and female control rats as well as in male and female rats with acute ( P ≤ 0.05) or chronic ( P ≤ 0.01 or P ≤ 0.05, respectively) CYP-induced cystitis. Void volume also increased in female control rats ( P ≤ 0.01) and female rats with acute ( P ≤ 0.05) or chronic ( P ≤ 0.05) CYP-induced cystitis as well as in male control rats ( P ≤ 0.05) and male rats with chronic CYP-induced cystitis ( P ≤ 0.01). These data suggest that VEGF may be a biomarker for interstitial cystitis/bladder pain syndrome and that targeting VEGF/VEGFR2 signaling may be an effective treatment.