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

        Misa Nakamura,Takashi Ozaki,Aiko Ishii,Masayoshi Konishi,Yuji Tsubota,Toru Furui,Hayato Tsuda,Ichiro Mori,Kiichiro Ota,Kennichi Kakudo 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.5

        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 (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.

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        Clinical outcome in patients with hand lesions associated with complex regional pain syndrome after arthroscopic rotator cuff repair

        Takaki Imai,Masafumi Gotoh,Keiji Fukuda,Misa Ogino,Hidehiro Nakamura,Hiroki Ohzono,Naoto Shiba,Takahiro Okawa 대한견주관절의학회 2021 대한견주관절의학회지 Vol.24 No.2

        Background: Complex regional pain syndrome (CRPS)-related hand lesions are one of the complications following arthroscopic rotator cuff repair (ARCR). This study aimed to investigate the clinical outcomes of patients with CRPS-related hand lesions following ARCR. Methods: Altogether, 103 patients with ARCR were included in this study (mean age, 63.6±8.2 years; 66 males and 37 females; follow-up period, preoperative to 12 months postoperative). Clinical assessment included the Japanese Orthopaedic Association (JOA) score, University of California, Los Angeles (UCLA) score, Constant score, 36-item short form health survey (SF-36) score, and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score from preoperative to 12 months postoperatively. The patients were either assigned to the CRPS group or non-CRPS group depending on CRPS diagnosis until the final follow-up, and clinical outcomes were then compared between the groups. Results: Of 103 patients, 20 (19.4%) had CRPS-related hand lesions that developed entirely within 2 months postoperatively. Both groups showed significant improvement in JOA, UCLA, and Constant scores preoperatively to 12 months postoperatively (p<001). Comparisons between the two groups were not significantly different, except for SF-36 “general health perception” (p<0.05) at 12 months postoperatively. At final follow-up, three patients had residual CRPS-related hand lesions with limited range of motion and finger edema. Conclusions: CRPS-related hand lesions developed in 19.4% of patients following ARCR. Shoulder or upper-limb function improved in most cases at 12 months, with satisfactory SF-36 patient-based evaluation results. Patients with residual CRPS-related hand lesions at the last follow-up require long-term follow-up.

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