Calcitonin induces connective tissue growth factor through ERK1/2 signaling in renal tubular cells

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.

Calcitonin induces connective tissue growth factor through ERK1/2 signaling in renal tubular cells

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.

Effects of aging on force adaptation during manipulation of a small object using a precision grip / 体力科学

The effects of aging on adaptive force control of precision grip while manipulating a small object were compared between older (84.2±8.9 yrs, n=33) and young adults (19.1±0.24 yrs, n=18) from the following perspectives: (1) adaptation to an unfamiliar object with uncertain physical properties during 16 consecutive lifts ; (2) adaptation to an object with a non-slippery (sandpaper) surface during 12 consecutive lifts, followed by 12 consecutive lifts with a slippery (silk) surface ; and (3) adaptation to objects with different weights (0.49, 0.98, 1.96 and 2.94 N) during 24 lifts (6 consecutive lifts for each weight) .During each trial, grip and load forces were monitored. Safety margin force and slip force were evaluated from the data obtained.<BR>The majority of older adults employed a considerably greater safety margin for an unfamiliar object in the initial trials than did young adults, while the minority of the older adults were able to adapt their safety margin force with a few trials, like the young adults. The older adults who overestimated the safety margin force, however, successfully adjusted their grip force to more optimal levels with repeated lifts, suggesting that the adaptive capability of grip force remained even at 90 years of age. The adaptation of older adults, however, was found to be slower (i. e., required more trials) than that of young adults. Upon encountering surface friction change, the safety margin forces in older adults were more strongly affected by the previous surface condition than those in the young adults. In addition, adaptation to a non-slippery surface seemed more difficult than that to a slippery surface with aging. Upon encountering weight change, older adults showed more difficulties in scaling their safety margin forces according to object weights.<BR>Slower adaptation and difficulty in adaptation to the friction or weight change in older adults may reflect the agerelated decline of tactile sensitivity which impaired the signaling of frictional conditions and various discrete events in the hand. In addition, the lift repetition for force adaptation may possibly reflect the age-related deficit or slowing of central processing capacities related to grip force production.