Propionate promotes vitamin D receptor expression via yes-associated protein in rats with short bowel syndrome

Vitamin D deficiency and refractory osteoporosis are common complications in patients with short bowel syndrome (SBS). The symptom of bone loss is not effectively alleviated, even after the oral administration of vitamin D in SBS patients who had been weaned off parenteral nutrition. In this study, we aimed to investigate the effect of propionate on the expression of the vitamin D receptor (VDR) in the small intestine of rats with SBS. Firstly, IEC-6 (intestinal epithelioid cell line No. 6) cells were incubated in vitro with 1 mM sodium propionate for 24 h. This resulted in a significant increase in the expression of VDR and yes-associated protein (YAP) compared with that in the control group. Transfection of IEC-6 cells with YAP siRNA significantly down-regulated the expression of VDR. By contrast, after incubating IEC-6 cells with lysophosphatidic acid, an agonist of YAP, upregulation of VDR and YAP was observed. Next, we investigated whether this effect occurs in vivo. Five-week-old male Sprague-Dawley rats underwent 80% small bowel resection to establish an SBS model. Rats treated with 1% w/v sodium propionate had high levels of VDR and YAP expression in the intestine and intestinal adaptation was clearly observed compared to the control group. However, these effects were blocked by intraperitoneal injection of verteporfin. Thus, this study showed that propionate promoted VDR expression in the intestine via the activity of YAP, both in vitro and in vivo. Moreover, propionate was shown to play an active role in postoperative intestinal adaptation in SBS rats.