Regulation of PDGFR⁺ cells and ICC in progesterone-mediated slow colon transit in pregnant mice

Background: Progesterone can inhibit intestinal smooth muscle contraction; however, the specific mechanism remains unclear. Besides smooth muscle cells, smooth muscle has two important mesenchymal cells, namely interstitial cells of Cajal (ICC) and PDGFR alpha(+) cells, which induce the contraction and relaxation of smooth muscles. We aimed to explore the regulation of PDGFR alpha(+) cells and ICC in progesterone-mediated colon slow transit in pregnant mice. Methods: Colon transit experiments were performed in vivo and in vitro to observe slow colon transit. The expression of PDGFR alpha and c-KIT was detected by Western blot, RT-PCR, and immunofluorescence. An isometric tension experiment was performed to investigate smooth muscle contractions. Results: The colon transit time in pregnant mice was longer than that in non-pregnant mice. Progesterone significantly blocks colonic smooth muscle contractions. However, when the relaxation and contraction of PDGFR alpha(+) cells and ICC are blocked, progesterone cannot inhibit smooth muscle contraction. When the function of only PDGFR alpha(+) cells are blocked, progesterone has a more obvious inhibitory effect on smooth muscle in the non-pregnant group than that in the pregnant group. However, when ICC alone was blocked, progesterone inhibited smooth muscle contractions more clearly in pregnant mice. The protein and mRNA expression of PDGFR alpha was higher and c-KIT was lower in pregnant mice. PDGFR alpha+ cells and ICC from smooth muscle all colocalize progesterone receptors. Conclusions: Under the regulation of progesterone, the relaxation function of PDGFR alpha(+) cells is enhanced and the contraction function of ICC is weakened, leading to the slow colon transit of pregnant mice.